The alarming rise in antibiotic resistance has led to an increase in patient mortality and health care costs. This problem is compounded by the absence of new antibiotics close to regulatory approval. Acinetobacter baumannii is a human pathogen that causes infections primarily in patients in intensive care units (ICUs) and is highly antibiotic resistant. Colistin is one of the last-line antibiotics for treating A. baumannii infections; however, colistin-resistant strains are becoming increasingly common. This cationic antibiotic attacks negatively charged bacterial membranes in a manner similar to that seen with cationic antimicrobials of the innate immune system. We therefore set out to determine if the increasing use of colistin, and emergence of colistin-resistant strains, is concomitant with the generation of cross-resistance to host cationic antimicrobials. We found that there is indeed a positive correlation between resistance to colistin and resistance to the host antimicrobials LL-37 and lysozyme among clinical isolates. Importantly, isolates obtained before and after treatment of individual patients demonstrated that colistin use correlated with increased resistance to cationic host antimicrobials. These data reveal the overlooked risk of inducing cross-resistance to host antimicrobials when treating patients with colistin as a last-line antibiotic. IMPORTANCE Increased use of the cationic antibiotic colistin to treat multidrug-resistant Acinetobacter baumannii has led to the development of colistin-resistant strains. Here we report that treatment of patients with colistin can induce not only increased resistance to colistin but also resistance to host cationic antimicrobials. This worrisome finding likely represents an example of a broader trend observed in other bacteria against which colistin is used therapeutically such as Pseudomonas aeruginosa and Klebsiella pneumoniae. Furthermore, these data suggest that the possible future use of an array of cationic antimicrobial peptides in development as therapeutics may have unintended negative consequences, eventually leading to the generation of hypervirulent strains that are resistant to innate host defenses. The potential for the induction of cross-resistance to innate immune antimicrobials should be considered during the development of new therapeutics.

Standard tuberculosis case reporting captures incarceration at diagnosis only. This retrospective analysis of 106 US-born adults with prevalent tuberculosis in 2011 found that 46.2% had documented histories of being in jail or prison, including 16.0% during the year before diagnosis.

INTRODUCTION: The purpose of this study was to examine community-associated methicillin resistant Staphylococcus aureus (CA-MRSA) carriage and infections and determine risk factors associated specifically with MRSA USA300. METHODS: We conducted a case control study in a pediatric emergency department. Nasal and axillary swabs were collected, and participants were interviewed for risk factors. The primary outcome was the proportion of S. aureus carriers among those presenting with and without a skin and soft tissue infection (SSTI). We further categorized S. aureus carriers into MRSA USA300 carriers or non-MRSA USA300 carriers. RESULTS: We found the MRSA USA300 carriage rate was higher in children less than two years of age, those with an SSTI, children with recent antibiotic use, and those with a family history of SSTI. MRSA USA300 carriers were also more likely to have lower income compared to non-MRSA USA300 carriers and no S. aureus carriers. Rates of Panton-Valentine leukocidin (PVL) genes were higher in MRSA carriage isolates with an SSTI, compared to MRSA carriage isolates of patients without an SSTI. There was an association between MRSA USA300 carriage and presence of PVL in those diagnosed with an abscess. CONCLUSION: Children younger than two years were at highest risk for MRSA USA300 carriage. Lower income, recent antibiotic use, and previous or family history of SSTI were risk factors for MRSA USA300 carriage. There is a high association between MRSA USA300 nasal/axillary carriage and presence of PVL in those with abscesses.

Evidence-based interventions for Staphylococcus aureus bacteremia (SAB) are well known, but it is unclear how they are implemented among patients with injection drug use-associated (IDU) SAB. Of 46 patients with IDU-SAB identified, all received high-quality SAB management; however, few received appropriate recognition or treatment of their underlying substance use disorder.

Among 283 symptomatic healthcare personnel (HCP) tested for SARS-CoV-2, 51 (18%) were positive. Among those 51 HCP, self reported loss of smell and taste were present in 51% and 52.9%, respectively, with either present in 60.8%. These symptoms had high specificity (93% each, 96% for either) for a positive SARS-CoV-2 test.

Two billion people worldwide are estimated to be latently infected with Mycobacterium tuberculosis (Mtb) and are at risk for developing active tuberculosis since Mtb can reactivate to cause TB disease in immune-compromised hosts. Individuals with latent Mtb infection (LTBI) and BCG-vaccinated individuals who are uninfected with Mtb, harbor antigen-specific memory CD4+ T cells. However, the differences between long-lived memory CD4+ T cells induced by latent Mtb infection (LTBI) versus BCG vaccination are unclear. In this study, we characterized the immune phenotype and functionality of antigen-specific memory CD4+ T cells in healthy BCG-vaccinated individuals who were either infected (LTBI) or uninfected (BCG) with Mtb. Individuals were classified into LTBI and BCG groups based on IFN-γ ELISPOT using cell wall antigens and ESAT-6/CFP-10 peptides. We show that LTBI individuals harbored high frequencies of late-stage differentiated (CD45RA−CD27−) antigen-specific effector memory CD4+ T cells that expressed PD-1. In contrast, BCG individuals had primarily early-stage (CD45RA−CD27+) cells with low PD-1 expression. CD27+ and CD27− as well as PD-1+ and PD-1− antigen-specific subsets were polyfunctional, suggesting that loss of CD27 expression and up-regulation of PD-1 did not compromise their capacity to produce IFN-γ, TNF-α and IL-2. PD-1 was preferentially expressed on CD27− antigen-specific CD4+ T cells, indicating that PD-1 is associated with the stage of differentiation. Using statistical models, we determined that CD27 and PD-1 predicted LTBI versus BCG status in healthy individuals and distinguished LTBI individuals from those who had clinically resolved Mtb infection after anti-tuberculosis treatment. This study shows that CD4+ memory responses induced by latent Mtb infection, BCG vaccination and clinically resolved Mtb infection are immunologically distinct. Our data suggest that differentiation into CD27−PD-1+ subsets in LTBI is driven by Mtb antigenic stimulation in vivo and that CD27 and PD-1 have the potential to improve our ability to evaluate true LTBI status.

Background.Significant progress has been made in reducing methicillin-resistant Staphylococcus aureus (MRSA) infections among hospitalized patients. However, the decreases in invasive MRSA infections among recently discharged patients have been less substantial. To inform prevention strategies, we assessed risk factors for invasive MRSA infection after acute-care hospitalizations. Methods.We conducted a prospective, matched case-control study. A case was defined as MRSA cultured from a normally sterile body site in a patient discharged from a hospital within the prior 12 weeks. Eligible case patients were identified from 15 hospitals across 6 US states. For each case patient, 2 controls were matched for hospital, month of discharge, and age group. Medical record reviews and telephone interviews were performed. Conditional logistic regression was used to identify independent risk factors for postdischarge invasive MRSA. Results.From 1 February 2011 through 31 March 2013, 194 case patients and 388 matched controls were enrolled. The median time between hospital discharge and positive culture was 23 days (range, 1-83 days). Factors independently associated with postdischarge MRSA infection included MRSA colonization (matched odds ratio [mOR], 7.71; 95% confidence interval [CI], 3.60-16.51), discharge to a nursing home (mOR, 2.65; 95% CI, 1.41-4.99), presence of a chronic wound during the postdischarge period (mOR, 4.41; 95% CI, 2.14-9.09), and discharge with a central venous catheter (mOR, 2.16; 95% CI, 1.13-4.99) or a different invasive device (mOR, 3.03; 95% CI, 1.24-7.39) in place. Conclusions.Prevention efforts should target patients with MRSA colonization or those with invasive devices or chronic wounds at hospital discharge. In addition, MRSA prevention efforts in nursing homes are warranted.

Following large declines in tuberculosis transmission the United States, large-scale screening programs targeting low-risk healthcare workers are increasingly a source of false-positive results. We report a large cluster of presumed false-positive tuberculin skin test results in healthcare workers following a change to 50-dose vials of Tubersol tuberculin.

Background: Use of nucleic acid amplification tests (NAAT) for the diagnosis of Mycobacterium tuberculosis (TB) has been recommended on respiratory specimens submitted for acid-fast bacilli (AFB) testing. It also helps distinguish between TB and non-tuberculous mycobacteria (NTM) species in a setting where NTM rates are relatively high. The purposes of this study are to describe the trend and characteristics of all AFB smear-positive respiratory samples that underwent amplified Mycobacterium tuberculosis direct (MTD) testing, a type of NAAT, and to evaluate the clinical utility and necessity of the test for diagnosis of TB in a population with high-HIV prevalence.

Purpose: To estimate the association between diabetes mellitus (DM) and all-cause mortality during tuberculosis (TB) treatment. Methods: From 2009 to 2012, a retrospective cohort study among reported TB cases in Georgia was conducted. Patients aged 16 years or older were classified by DM and human immunodeficiency virus (HIV) status at the time of TB diagnosis and followed during TB treatment to assess mortality. Hazard ratios were used to estimate the association between DM and death. Results: Among 1325 patients with TB disease, 151 (11.4%) had DM, 147 (11.1%) were HIV-infected, and seven (0.5%) had both DM and HIV. Patients with TB-DM were more likely to have cavitary lung disease compared with those with TB alone (51.0% vs. 34.7%) and those with TB-HIV were more likely to have military/disseminated disease (12.9% vs. 3.4%) and resistance to rifampin or isoniazid (21.8% vs. 9.0%) compared with those without HIV infection (P < .05). In multivariable analysis, DM was not associated with death during TB treatment (hazard ratio, 1.22; 95% confidence interval, 0.70-2.12) or any death (adjusted odds ratio, 1.05; 95% confidence interval, 0.60-1.84). Conclusions: Among TB patients in Georgia, the prevalence of comorbid DM and coinfection with HIV was nearly identical. In adjusted models, TB patients with DM did not have increased risk of all-cause mortality.