Altered monocyte phenotypes but not impaired peripheral T cell immunity may explain susceptibility of the elderly to develop tuberculosis.

Tuberculosis (TB) is the leading killer due to a single infectious disease worldwide. With the aging of the global population, the case rate and deaths due to TB are highest in the elderly population. While general immunosenescence associated with old age is thought to contribute to the susceptibility of the elderly to develop active TB disease, very few studies of immune function in elderly individuals with Mycobacterium tuberculosis (M.tb) infection or disease have been performed. In particular, impaired adaptive T cell immunity to M.tb is one proposed mechanism for the elderly's increased susceptibility primarily on the basis of the decreased delayed type hypersensitivity response to tuberculin-purified protein derivative in the skin of elderly individuals. To investigate immunological reasons why the elderly are susceptible to develop active TB disease, we performed a cross-sectional observational study over a five year period (2012-2016) enrolling participants from 2 age groups (adults: 25-44 years; elderly: 65 and older) and 3 M.tb infection statuses (active TB, latent TB infection, and healthy controls without history of M.tb infection). We hypothesized that impaired peripheral T cell immunity plays a role in the biological susceptibility of the elderly to TB. Contrary to our hypothesis, we observed no evidence of impaired M.tb specific T cell frequency or altered production of cytokines implicated in M.tb control (IFN-γ, IL-10) in peripheral blood in the elderly. Instead, we observed alterations in monocyte proportion and phenotype with age and M.tb infection that suggest their potential role in the susceptibility of the elderly to develop active TB. Our results suggest a potential link between the known widespread low-grade systemic inflammation of old age, termed "inflammaging," with the elderly's specific susceptibility to developing active TB. Moreover, our results highlight the need for further research into the biological reasons why the elderly are more susceptible to disease and death from TB, so that public health systems can be better equipped to face the present and future problem of TB in an aging global population.

Risk factors and acute in-hospital costs for infected pressure ulcers among gunshot-spinal cord injury victims in southeastern Michigan.

BACKGROUND: Management of pressure ulcers (PrUs) in patients with gunshot-spinal cord injuries (SCIs) presents unique medical and economic challenges for practitioners. METHODS: A retrospective chart review was conducted at 3 acute care hospitals in metropolitan Detroit for patients admitted with PrUs due to gunshot-SCIs between January 2004 and December 2008. Multivariate analysis using logistic regression was conducted to choose for the independent predictors of infected PrUs. Mean adjusted in-hospital costs per patient and per hospitalization were calculated and compared between infected and noninfected PrUs. RESULTS: The study cohort included 201 gunshot-SCI patients with PrUs contributing to 395 admissions, including readmissions, between 2004 and 2008. Seventy-six patients (38%) had infected PrUs at time of the index admission. Independent predictors of infected PrUs on index admission included Charlson Comorbidity Index ≥2 (odds ratio, 2.18, P = .026) and stage III/IV PrU (odds ratio, 4.82; P <.0001). During the study period, the cumulative median duration of hospitalization per patient was 12 days (interquartile range, 6-24 days), resulting in a mean adjusted cost of $19,969 ± $6639 per patient. The mean adjusted cost per hospitalization for patients with infected PrUs was significantly higher than that for patients with noninfected PrUs ($16,735 ± $8310 vs $12,356 ± $7007; P <.001). CONCLUSIONS: A multidisciplinary approach including home-based rehabilitation programs and SCI wound clinics might help prevent PrUs and their complications and reduce associated costs.

Risk factors for bloodstream infection caused by extended-spectrum ß-lactamase-producing Escherichia coli and Klebsiella pneumoniae: A focus on antimicrobials including cefepime.

BACKGROUND: Extended-spectrum ß-lactamase (ESBL)-producing pathogens represent increasing challenges to physicians because of rising prevalence, high mortality, and challenging treatment. Identifying high risks and early appropriate therapy is critical to favorable outcomes. METHODS: This is a 5-year retrospective case-case-control study performed at the Detroit Medical Center on adult patients with bloodstream infection (BSI) caused by ESBL-producing and non-ESBL-producing Escherichia coli or Klebsiella pneumoniae, each compared with uninfected controls. Data were collected from December 2004-August 2009. Multivariate analysis was performed using logistic regression. RESULTS: Participants included 103 patients with BSI caused by ESBL-producing pathogens and 79 patients with BSI caused by pathogens that did not produce ESBLs. The mean age of patients in the ESBL group was 67 years; of the patients, 51% were men, 77% were black, and 38% (n = 39) died in hospital. The mean age of patients in the non-ESBL group was 58 years; of the patients, 51% were men, 92% were black, and 22% (n = 17) died in hospital. On multivariate analysis, predictors of BSI caused by ESBL-producing pathogens included central venous catheter (odds ratio [OR], 29.4; 95% confidence interval [CI], 3.0-288.3), prior ß-lactam-/ß-lactamase-inhibitor therapy (OR, 28.1; 95% CI, 1.99-396.5), and prior cefepime therapy (OR, 22.7; 95% CI, 2.7-192.4). The only risk factor for BSI caused by non-ESBL-producing pathogens was urinary catheter insertion (OR, 18.2; 95% CI, 3.3-100.3). CONCLUSION: Prior antimicrobial therapy, particularly with ß-lactam, was the strongest unique risk factor for BSI caused by ESBL-producing E coli or K pneumoniae.

Risk factors and outcomes for patients with bloodstream infection due to Acinetobacter baumannii-calcoaceticus complex.

Identifying patients at risk for bloodstream infection (BSI) due to Acinetobacter baumannii-Acinetobacter calcoaceticus complex (ABC) and providing early appropriate therapy are critical for improving patient outcomes. A retrospective matched case-control study was conducted to investigate the risk factors for BSI due to ABC in patients admitted to the Detroit Medical Center (DMC) between January 2006 and April 2009. The cases were patients with BSI due to ABC; the controls were patients not infected with ABC. Potential risk factors were collected 30 days prior to the ABC-positive culture date for the cases and 30 days prior to admission for the controls. A total of 245 case patients were matched with 245 control patients. Independent risk factors associated with BSI due to ABC included a Charlson's comorbidity score of ≥ 3 (odds ratio [OR], 2.34; P = 0.001), a direct admission from another health care facility (OR, 4.63; P < 0.0001), a prior hospitalization (OR, 3.11; P < 0.0001), the presence of an indwelling central venous line (OR, 2.75; P = 0.011), the receipt of total parenteral nutrition (OR, 21.2; P < 0.0001), the prior receipt of ß-lactams (OR, 3.58; P < 0.0001), the prior receipt of carbapenems (OR, 3.18; P = 0.006), and the prior receipt of chemotherapy (OR, 15.42; P < 0.0001). The median time from the ABC-positive culture date to the initiation of the appropriate antimicrobial therapy was 2 days (interquartile range [IQR], 1 to 3 days). The in-hospital mortality rate was significantly higher among case patients than among control patients (OR, 3.40; P < 0.0001). BSIs due to ABC are more common among critically ill and debilitated institutionalized patients, who are heavily exposed to health care settings and invasive devices.

Epidemiology of vancomycin-resistant enterococci with reduced susceptibility to daptomycin.

A retrospective case-case control study was conducted, including 60 cases with daptomycin-nonsusceptible vancomycin-resistant enterococci (DNS-VRE) matched to cases with daptomycin-susceptible VRE and to uninfected controls (1∶1∶3 ratio). Immunosuppression, presence of comorbid conditions, and prior exposure to antimicrobials were independent predictors of DNS-VRE, although prior daptomycin exposure occurred rarely. In summary, a case-case control study identified independent risk factors for the isolation of DNS-VRE: immunosuppression, multiple comorbid conditions, and prior exposures to cephalosporines and metronidazole.

Comparison of the clinical characteristics and outcomes associated with vancomycin-resistant Enterococcus faecalis and vancomycin-resistant E. faecium bacteremia.

In published studies, cohorts of patients with bacteremia due to vancomycin-resistant Enterococcus (VRE) have predominantly been infected with Enterococcus faecium. Little is known about the epidemiology and outcomes associated with bacteremia due to VR Enterococcus faecalis. A retrospective study of isolates obtained from January 2008 to October 2010 was conducted at Detroit Medical Center (DMC). Unique patients with blood cultures positive for VRE were reviewed. Outcomes were analyzed using logistic regression. During the study period, 105 cases of bacteremia due to VR E. faecalis and 197 cases of bacteremia due to VR E. faecium were identified. The mean age in the study cohort was 61.5 ± 15 years; 162 subjects (53.6%) were male. After controlling for a propensity score, bacteremia due to VR E. faecalis was associated with >2-fold-lower in-hospital mortality than bacteremia due to VR E. faecium. Interestingly, bacteremia due to VR E. faecalis was associated with longer hospital stay after VRE isolation, although total length of stay was similar for groups with VR E. faecalis and VR E. faecium. Bacteremia due to VR E. faecalis was associated with a >2-fold-lower risk for mortality than bacteremia due to VR E. faecium, possibly due to the availability of ß-lactam therapeutics for treatment of VR E. faecalis.