Kimberly A. Shriner

Regulatory Oversight and Safety of Probiotic Use

Saccharomyces boulardii probiotics should be used with caution for management of Clostridium difficile infections in hospitalized patients.

Evidence of reduced glutamate in the frontal lobe of HIV-seropositive patients†

Neurological complications associated with the acquired immunodeficiency syndrome, in particular, HIV‐associated dementia, continue to plague those infected. We report our finding that the concentration of brain Glu is reduced in the frontal white matter region in this condition. In addition, our data appear to absolve highly active retroviral therapy (HAART) from blame, as drug‐naïve patients were equally affected. Our findings suggest that Glu neurotransmission is abnormal and may be a key target for early interventions to reduce the later incidence of neurocognitive impairment and dementia among HIV‐seropositive patients. Copyright

Risk of developing pneumonia is enhanced by the combined traits of fluoroquinolone resistance and type III secretion virulence in respiratory isolates of Pseudomonas aeruginosa.

Objectives:To determine the differential association of host characteristics, antimicrobial resistance, and type III secretion system virulence of Pseudomonas aeruginosa isolates with respiratory syndromes in hospitalized adult patients. Design:Retrospective, cohort study. Setting:Community teaching hospital. Patients:Two hundred eighteen consecutive adult patients with respiratory culture positive for P. aeruginosa between January 2005 to January 2010. Interventions:Medical charts were reviewed to obtain demographic, laboratory, radiographic, and clinical information. Isolates were assayed by polymerase chain reaction for genes encoding the type III secretion system effectors (ExoU, ExoS, and PcrV) and for strain relatedness using randomly amplified polymorphic DNA analysis. Levofloxacin susceptibility was determined by broth microdilution. Patients were grouped by colonization, bronchitis, or pneumonia and were compared for differential risk of developing the clinical syndrome with respect to host and microbial characteristics. Measurements and Main Results:Half of the study cohort (54%, 117 of 218) had pneumonia, 32% (70 of 218) had bronchitis, and 14% (31 of 218) had colonization; in-hospital mortality was 35%, 11%, and 0%, respectively. Host factors strongly associated with pneumonia development were residence in long-term care facility, healthcare-associated acquisition of P. aeruginosa, higher Acute Physiology and Chronic Health Evaluation II score, presence of enteral feeding tube, mechanical ventilation, and recent history of pneumonia. Fluoroquinolone-resistant (57% vs 34%, 16%; p < 0.0001) and multidrug-resistant (36% vs 26%, 7%; p = 0.0045) strains were more likely to cause pneumonia than bronchitis or colonization, respectively. Analysis of host and microbial factors in a multivariate regression model yielded the combined traits of fluoroquinolone resistance and gene encoding the type III secretion system ExoU effector in P. aeruginosa as the single most significant predictor of pneumonia development. Conclusions:These results suggest that fluoroquinolone-resistant phenotype in a type III secretion system exoU strain background contributes toward the pathogenesis of P. aeruginosa in pneumonia.

Reducing empirical use of fluoroquinolones for Pseudomonas aeruginosa infections improves outcome.

BACKGROUND We previously reported ciprofloxacin resistance (CR) and empirical use of fluoroquinolones as predictors of mortality in patients infected with Pseudomonas aeruginosa in a case-control study. Here, we assessed the clinical impact of reducing empirical fluoroquinolone use for P. aeruginosa infections in hospitalized patients by performing a follow-up study in 2005-06 [period 2 (P2)] and comparing this with prior data from 2001-02 [period 1 (P1)]. METHODS Medical charts of infected patients who received at least 72 h of antibiotic therapy were reviewed. Patients were subgrouped based on the susceptibility of infected strains into the CR or ciprofloxacin-susceptible group. Antibiograms, patient and treatment variables and outcome measures were compared between groups and between study periods. RESULTS Study patients were elderly (median age, 76 years), had a median of three co-morbidities and a median APACHE II score of 13. Most (75%) had pneumonia or urosepsis. Empirical use of fluoroquinolones was reduced by 30% in P2 versus P1, with a corresponding 39% increase in piperacillin/tazobactam use. The resultant positive impact observed in the CR group during P2 includes shortened delay to receipt of effective therapy (1 versus 3.5 days, P < 0.0001), reduced length of stay (13 versus 16 days, P = 0.03) and 2-fold lower mortality (9% versus 22%, P = 0.05). Susceptibility of P. aeruginosa improved by 10% to all antipseudomonal agents tested. CONCLUSIONS In settings where high rates of fluoroquinolone resistance exist, use of non-fluoroquinolone-based empirical regimens for P. aeruginosa infections improves patient outcomes and organism susceptibility over time.

Can clinical and molecular epidemiologic parameters guide empiric treatment with vancomycin for methicillin-resistant Staphylococcus aureus infections?☆☆☆

Reports of vancomycin treatment failure for infections caused by susceptible methicillin-resistant Staphylococcus aureus (MRSA) strains with elevated minimum inhibitory concentration (MIC) has prompted use of high-dose therapy, but nephrotoxicity is a concern. We determined whether clinical and molecular epidemiologic parameters can be used to guide empiric vancomycin therapy and strain susceptibility to alternative agents. Medical charts of 180 hospitalized adults with MRSA infections were reviewed. MICs of vancomycin, daptomycin, linezolid, and tigecycline were determined by Etest. Patient isolates were assayed for genes encoding Panton-Valentine leukocidin (PVL) and SCCmec type. High vancomycin MIC did not correlate with place of acquisition, invasiveness of infection, or history of health care exposure. High MIC was present in 32% of strains overall and in 23% of PVL+, SCCmec IV strains; all were susceptible to alternative agents. Clinicians should not make empiric treatment decisions related to vancomycin use based on history of healthcare exposure risk or residence at onset of infection for patients hospitalized with MRSA infections.

Distinguishing Brain Impact of Aging and HIV Severity in Chronic HIV Using Multiparametric MR Imaging and MR Spectroscopy

Abstract Background Combination antiretroviral therapy (cART) has transformed HIV into a manageable but complex chronic disease, in which it is uncertain which brain insults may relate to age vs initial disease severity. We evaluate N-acetyl-aspartate/creatine (NAA/Cr), white matter hyperintensities (WMH), and mean cortical thickness to identify which subclinical markers of brain insult best relate to CD4 nadir and aging. This is a prospective study of the association between brain markers with age and initial infection severity, based on CD4 nadir, in chronic HIV patients. Methods Thirty-seven chronic HIV patients (age 25–77 years) with successful viral suppression were scanned on a GE 3T magnetic resonance imaging scanner to obtain NAA/Cr (standardized and averaged over 5 brain regions), log-transformed WMH volume, and mean cortical thickness. The brain measures were fitted with both CD4 nadir and age to evaluate the significance of their relationship. Results NAA/Cr, WMH, and cortical thickness were all correlated with age and CD4 nadir in unadjusted associations. Stepwise regression models showed that NAA/Cr alone best predicted CD4 nadir (β = 40.1 ± 13.3; P = .005), whereas WMH (β = 2.3 ± .9; P = .02) and mean cortical thickness (β = –2.7 ± 6.6; P < .0001) together produced the best model fit with age. NAA/Cr was higher for HIV stage 1 (CD4 nadir ≥ 500 cells/ µL; n = 15) compared with stage 2 (200 ≥ CD4 nadir < 500; n = 13) and stage 3 (CD4 nadir < 200; n = 9; P < .01 for both). Conclusions In patients with effectively suppressed HIV, NAA reflects the subclinical brain impact of initial disease severity related to development of even mild immune compromise, whereas cortical thickness and WMH volume are useful to evaluate age-related changes.