A substantial proportion of patients become colonised with Candida spp during hospital stay, but only few subsequently develop severe infection Clinical signs of severe infection manifest early but lack specificity until late in the course of the disease, thus representing a particular challenge for diagnosis Mostly nosocomial, invasive candidiasis occurs in only 1-8% of patients admitted to hospitals, but in around 10% of patients housed in intensive care units where it can represent up to 15% of all nosocomial infections We review the epidemiology of invasive candidiasis in non-immunocompromised, critically ill patients with special emphasis on disease trends over time, pathophysiology, diagnostic approach, risk factors, and impact Recent epidemiological data suggesting that the emergence of non-albicans candida strains with reduced susceptibility to azoles, previously linked to the use of new antifungals for empiric and prophylactic therapy in immunocompromised patients, may not have occurred in the critically ill Management of invasive candidiasis in these patients will be addressed in the December issue of The Lancet Infectious Diseases

https://www.thelancet.com/pdfs/journals/laninf/PIIS1473-3099(03)00801-6.pdf

Epidemiology of candida species infections in critically ill non-immunosuppressed patients

The body is host to a wide variety of microbial communities from which the immune system protects us and that are important for the normal development of the immune system and for the maintenance of healthy tissues and physiological processes. Investigators have mostly focused on the bacterial members of these communities, but fungi are increasingly being recognized to have a role in defining these communities and to interact with immune cells. In this Review, we discuss what is currently known about the makeup of fungal communities in the body and the features of the immune system that are particularly important for interacting with fungi at these sites.

The mycobiota: interactions between commensal fungi and the host immune system.

Background Unnecessary use of antimicrobials contributes to the emergence and dissemination of antimicrobial-resistant nosocomial pathogens in part through elimination of normal anaerobic bacterial flora that inhibit overgrowth of pathogenic microorganisms. Methods A prospective observational study was conducted in a 650-bed, university-affiliated hospital. All adult nonintensive care inpatients for whom new antimicrobials were prescribed during a 2-week period were monitored throughout their hospitalization. We examined how often antimicrobials, in particular those with antianaerobic activity, were used unnecessarily. The reasons for unnecessary therapy were assessed and common patterns of unnecessary use were identified. Results A total of 1941 antimicrobial days of therapy were prescribed for 129 patients. A total of 576 (30%) of the 1941 days of therapy were deemed unnecessary. The most common reasons for unnecessary therapy included administration of antimicrobials for longer than recommended durations (192 days of therapy), administration of antimicrobials for noninfectious or nonbacterial syndromes (187 days of therapy), and treatment of colonizing or contaminating microorganisms (94 days of therapy). Antianaerobic agents accounted for 203 (35%) of the 576 unnecessary antimicrobial days of therapy, and these agents were also frequently prescribed (98 days of therapy) when equally efficacious alternative regimens with minimal antianaerobic activity were available. Conclusions In our institution, hospitalized patients frequently received unnecessary antimicrobial therapy, and antianaerobic agents were often prescribed when this spectrum of activity was not indicated.

https://jamanetwork.com/journals/jamainternalmedicine/articlepdf/215446/ioi20477.pdf

Unnecessary use of antimicrobials in hospitalized patients: current patterns of misuse with an emphasis on the antianaerobic spectrum of activity

Increasingly, epidemiologic and clinical data support the hypothesis that perturbations in the gastrointestinal (GI) microbiota because of antibiotic use and dietary differences in 'industrialized' countries have disrupted the normal microbiota-mediated mechanisms of immunological tolerance in the mucosa, leading to an increase in the incidence of allergic airway disease. The data supporting this 'microflora hypothesis' includes correlations between allergic airway disease and (1) antibiotic use early in life, (2) altered fecal microbiota and (3) dietary changes over the past two decades. Our laboratory has recently demonstrated that mice can develop allergic airway responses to allergens if their endogenous microbiota is altered at the time of first allergen exposure. These experimental and clinical observations are consistent with other studies demonstrating that the endogenous microbiota plays a significant role in shaping the development of the immune system. Data are beginning to accumulate that a 'balanced' microbiota plays a positive role in maintaining mucosal immunologic tolerance long after post-natal development. Other studies have demonstrated that even small volumes delivered to the nasopharynx largely end up in the GI tract, suggesting that airway tolerance and oral tolerance may operate simultaneously. The mechanism of microbiota modulation of host immunity is not known; however, host and microbial oxylipins are one potential set of immunomodulatory molecules that may control mucosal tolerance. The cumulative data are beginning to support the notion that probiotic and prebiotic strategies be considered for patients coming off of antibiotic therapy.

/pdf/the-microflora-hypothesis-of-allergic-diseases-1rk8t28j7o.pdf

The ‘microflora hypothesis’ of allergic diseases

Andrew Koh and colleagues report that gut anaerobes in adult mice prevent Candida albicans colonization by inducing an antimicrobial peptide.

/pdf/activation-of-hif-1a-and-ll-37-by-commensal-bacteria-32ma8cd0gv.pdf

Activation of HIF-1α and LL-37 by commensal bacteria inhibits Candida albicans colonization

This study evaluated the effects of broad-spectrum antibiotics on the gastrointestinal (G.I.) yeast flora of humans and correlated the findings with those obtained from a mouse model of G.I. colonization by Candida albicans. We prospectively studied 46 adult cancer patients who received one of five broad-spectrum antibiotics (ceftriaxone, ceftazidime, ticarcillin-clavulanic acid, imipenem-cilastatin, and aztreonam) as therapy for infections. Quantitative examination of yeast colonization of stools was conducted at the baseline, at the end of antibiotic treatment, and 1 week after discontinuation of therapy. Antibiotics with anaerobic activity (ticarcillin-clavulanic acid) or high G.I. concentrations (ceftriaxone) caused a higher and more sustained increase in G.I. colonization by yeasts than did antibiotics with poor anaerobic activity (ceftazidime and aztreonam) or a low G.I. concentration (imipenem-cilastatin). These results were similar to those obtained with a mouse model of G.I. colonization by C. albicans that involved the same antibiotics. Hence, the mouse model may be useful for evaluation of yeast colonization of the human G.I. tract.

G Vrenzos

Papers

Prospective evaluation of effects of broad-spectrum antibiotics on gastrointestinal yeast colonization of humans.