Anticytokine Autoantibodies and Fungal Infections.

Anticytokine autoantibodies (ACAAs) can cause adult onset immunodeficiencies which mimic primary immunodeficiencies and can present as refractory and severe fungal infections. This paper provides an overview of the role of innate immunity, including key cytokines, in fungal infections and then describes four clinical scenarios where ACAAs are associated with severe presentations of a fungal infection: (1) infection and anti-interferon-γ, (2) histoplasmosis and anti-interferon-γ, (3) infection and anti-GM-CSF, and (4) mucocutaneous candidiasis and anti-IL-17A/F (IL-22). Testing for ACAAs and potential therapeutic options are discussed.

Piperacillin/tazobactam versus cefepime or carbapenems for cefoxitin-non-susceptible Enterobacter cloacae, Klebsiella aerogenes, Citrobacter freundii, Serratia marcescens and Morganella morganii bacteraemia in immunocompromised patients.

Background: The role of piperacillin/tazobactam for treatment of serious infections due to AmpC-producing organisms remains debatable, particularly in immunocompromised patients.

Methods: This was a retrospective cohort study in immunocompromised patients that investigated the effect of definitive treatment with either piperacillin/tazobactam versus cefepime or carbapenems for bacteraemia caused by cefoxitin-non-susceptible Enterobacterales. The primary endpoint was a composite of clinical and microbiological failure.

Risk factors and outcomes associated with persistent vancomycin resistant Enterococcal Bacteremia.

Background: Prior studies have identified that vancomycin resistant enterococcus (VRE) bacteremia that persists for four days or more is an independent predictor of mortality. Despite this, there is no published data to identify those patients at highest risk of developing persistent VRE bacteremia.

Methods: This was a single center, retrospective, case-control study of adult patients with a VRE bloodstream infection (BSI).

Coccidioides Species: A Review of Basic Research: 2022.

and are closely related fungal species that cause coccidioidomycosis. These dimorphic organisms cause disease in immunocompetent as well as immunocompromised individuals and as much as 40% of the population is infected in the endemic area. Although most infections resolve spontaneously, the infection can be prolonged and, in some instances, fatal.

Sustained Reduction in Urgent Care Antibiotic Prescribing During the Coronavirus Disease 2019 Pandemic: An Academic Medical Center's Experience.

We compared antibiotic prescribing before and during the -coronavirus disease 2019 (COVID-19) pandemic at 2 academic urgent care clinics and found a sustained decrease in prescribing driven by respiratory encounters and despite transitioning to telemedicine. Antibiotics were rarely prescribed during encounters for COVID-19 or COVID-19 symptoms. COVID-19 revealed opportunities for outpatient stewardship programs.

Cost-effectiveness of bezlotoxumab and fidaxomicin for initial Clostridioides difficile infection.

Objectives: Treatment of Clostridioides difficile infection (CDI) has undergone significant change in recent years with the introduction of fidaxomicin and bezlotoxumab. This study evaluated the cost-effectiveness of fidaxomicin and bezlotoxumab for initial CDI compared with standard therapy with oral vancomycin.

Methods: A Markov model with eight health states was built based on transition probabilities, costs and health utilities derived from literature to evaluate the cost-effectiveness of standard fidaxomicin, bezlotoxumab plus vancomycin, and extended-pulsed fidaxomicin versus standard oral vancomycin over a lifetime horizon from the US societal perspective.

Significance of bacterial and viral genotypes as a risk factor in driving cancer (Review).

Microbes have been known to drive human cancers for over half a century. However, despite the association of bacterial and viral infections with a high risk of cancer, most infections do not result in the development of cancer. Additionally, certain bacteria and viruses, considered to drive oncogenesis, are commonly prevalent in the global population.

Impact of Rapid Antimicrobial Susceptibility Testing in Gram-Negative Rod Bacteremia: a Quasi-experimental Study.

Clinical justification for rapid antimicrobial susceptibility testing (AST) in Gram-negative rod (GNR) bacteremia is compelling; however, evidence supporting its value is sparse. We investigated the impact of rapid AST on clinical and antimicrobial stewardship outcomes in real-world practice. We performed a before-and-after quasi-experimental study from February 2018 to July 2019 at a tertiary hospital of the 24-h/day, 7-day/week implementation of the direct Vitek 2 AST method from positive blood culture broth for GNR bacteremia with electronic isolate-specific de-escalation comments and daytime antibiotic stewardship program (ASP) intervention.

Vancomycin-resistant enterococcus infection in the hematopoietic stem cell transplant recipient: an overview of epidemiology, management, and prevention.

Vancomycin-resistant (VRE) is now one of the leading causes of nosocomial infections in the United States. Hematopoietic stem cell transplantation (HSCT) recipients are at increased risk of VRE colonization and infection. VRE has emerged as a major cause of bacteremia in this population, raising important clinical questions regarding the role and impact of VRE colonization and infection in HSCT outcomes as well as the optimal means of prevention and treatment.

Accelerated aging of selective brain structures in human immunodeficiency virus infection: a controlled, longitudinal magnetic resonance imaging study.

Advances in treatment have transformed human immunodeficiency virus (HIV) infection from an inexorable march to severe morbidity and premature death to a manageable chronic condition, often marked by good health. Thus, infected individuals are living long enough that there is a potential for interaction with normal senescence effects on various organ systems, including the brain. To examine this interaction, the brains of 51 individuals with HIV infection and 65 uninfected controls were studied using 351 magnetic resonance imaging and a battery of neuropsychological tests collected 2 or more times over follow-up periods ranging from 6 months to 8 years.

Utility of DNA sequencing for direct identification of invasive fungi from fresh and formalin-fixed specimens.

Objectives: To describe and discuss the utility and potential pitfalls of ribosomal RNA locus sequencing for direct identification of invasive fungi from fresh and formalin-fixed, paraffin-embedded specimens.

Methods: DNA was extracted from fresh and formalin-fixed, paraffin-embedded tissue and subjected to real-time polymerase chain reaction (PCR) targeting ITS2 and D2 regions of fungal ribosomal RNA locus. Cycle sequencing was performed on PCR products, and the identity of sequences was determined using a public database.

Regional brain structural dysmorphology in human immunodeficiency virus infection: effects of acquired immune deficiency syndrome, alcoholism, and age.

Background: Human immunodeficiency virus (HIV) infection and alcoholism each carries liability for disruption of brain structure and function integrity. Despite considerable prevalence of HIV-alcoholism comorbidity, few studies examined the potentially heightened burden of disease comorbidity.

Methods: Participants were 342 men and women: 110 alcoholics, 59 with HIV infection, 65 with HIV infection and alcoholism, and 108 healthy control subjects.

Pontocerebellar contribution to postural instability and psychomotor slowing in HIV infection without dementia.

Postural instability occurs in HIV infection, but quantitative balance tests in conjunction with neuroimaging are lacking. We examined whether infratentorial brain tissue volume would be deficient in nondemented HIV-infected individuals and whether selective tissue deficits would be related to postural stability and psychomotor speed performance. The 123 participants included 28 men and 12 women with HIV infection without dementia or alcohol use disorders, and 40 men and 43 women without medical or psychiatric conditions.

Ceftobiprole: a new cephalosporin for the treatment of skin and skin structure infections.

Ceftobiprole is among the first of a new generation of cephalosporins with activity against aerobic Gram-negative bacilli, which extends to cefepime-sensitive Pseudomonas aeruginosa, and activity against Gram-positive organisms, which includes methicillin-resistant Staphylococcus aureus. Ceftobiprole is currently undergoing evaluation by the US FDA for the treatment of complicated skin and skin structure infections, with a decision pending further evaluation of study site monitoring. It is also being evaluated for the treatment of community-acquired and healthcare-associated pneumonia.

Frontostriatal fiber bundle compromise in HIV infection without dementia.

Background: Quantitative fiber tracking derived from diffusion tensor imaging (DTI) was used to determine whether white matter association, projection, or commissural tracts are affected in nondemented individuals with HIV infection and to identify the regional distribution of sparing and impairment of fiber systems.

Methods: DTI measured fractional anisotropy and diffusivity, quantified separately for longitudinal (lambdaL) diffusivity (index of axonal injury) and transverse (lambdaT) diffusivity (index of myelin injury), in 11 association and projection white matter tracts and six commissural tracts in 29 men and 13 women with HIV infection and 88 healthy, age-matched controls (42 men and 46 women).

Results: The total group of HIV-infected individuals had higher diffusivity (principally longitudinal) than controls in the posterior sectors of the corpus callosum, internal and external capsules, and superior cingulate bundles.

Expert opinion: what to do when there is Coccidioides exposure in a laboratory.

Inadvertent exposure to Coccidioides species by laboratory staff and others as a result of a mishap is not an uncommon cause of infection in clinical microbiology laboratories. These types of infection may occur in laboratories outside the endemic areas, because the etiologic agent is unexpected in the submitted specimens and because personnel may be unfamiliar with the hazards of dealing with Coccidioides species in the laboratory. Coccidioidal infections are often difficult to treat, and outcomes can be poor.

Management of infections due to KPC-producing Klebsiella pneumoniae.

The emergence of the Klebsiella pneumoniae carbapenemases in K. pneumoniae and other Gram-negative bacteria, usually on a background of multidrug resistance, has led to difficult therapeutic choices. Among available antibiotics, tigecycline and the polymyxins are the most frequently active against these organisms in vitro.

The efficacy and safety of ceftobiprole in the treatment of complicated skin and skin structure infections: evidence from 2 clinical trials.

Complicated skin and skin structure infections (cSSSIs) are common and are associated with significant health and economic costs. These infections are predominantly characterized by infection with Staphylococcus aureus, and SENTRY Surveillance data indicate that the occurrence of this pathogen in cSSSIs has increased and that almost half of the isolated pathogens are methicillin-resistant S. aureus (MRSA).

Upper and lower limb motor impairments in alcoholism, HIV infection, and their comorbidity.

Background: Both HIV infection and alcoholism can impair motor abilities involving manual dexterity and postural stability. Given the high prevalence of HIV and alcoholism comorbidity, we examined whether each disease selectively disrupts different components of upper and lower limb motor control and whether these impairments are compounded by disease comorbidity.

Methods: Simple and complex upper (speed and finger dexterity) and lower (static posture) limb functions were tested in 31 men with HIV infection, 27 with alcoholism, 43 comorbid for HIV infection and alcoholism, and 22 normal healthy controls to assess whether comorbid patients would demonstrate greater motor impairment relative to those with a single diagnosis.

Alcoholism, HIV infection, and their comorbidity: factors affecting self-rated health-related quality of life.

Objective: Both alcoholism and HIV infection reduce health-related quality of life (HRQOL), and their co-occurrence is highly prevalent. We sought to determine whether comorbidity for both disorders further reduced HRQOL and what factors exacerbated or mitigated their effect.

Method: HRQOL, CD4 T-cell counts, lifetime alcohol consumption and length of sobriety, depressive symptoms (Beck Depression Inventory [BDI]-II), general cognitive status (Peabody Picture Vocabulary Test II), and other psychiatric comorbidities were assessed in patients with alcohol dependence or abuse (n = 44), HIV infection (n = 44), alcohol + HIV (n = 55), and healthy controls (n = 41).