Candida colonization index and subsequent infection in critically ill surgical patients: 20 years later.

INTRODUCTION: For decades, clinicians dealing with immunocompromised and critically ill patients have perceived a link between Candida colonization and subsequent infection. However, the pathophysiological progression from colonization to infection was clearly established only through the formal description of the colonization index (CI) in critically ill patients. Unfortunately, the literature reflects intense confusion about the pathophysiology of invasive candidiasis and specific associated risk factors. METHODS: We review the contribution of the CI in the field of Candida infection and its development in the 20 years following its original description in 1994. The development of the CI enabled an improved understanding of the pathogenesis of invasive candidiasis and the use of targeted empirical antifungal therapy in subgroups of patients at increased risk for infection. RESULTS: The recognition of specific characteristics among underlying conditions, such as neutropenia, solid organ transplantation, and surgical and nonsurgical critical illness, has enabled the description of distinct epidemiological patterns in the development of invasive candidiasis. CONCLUSIONS: Despite its limited bedside practicality and before confirmation of potentially more accurate predictors, such as specific biomarkers, the CI remains an important way to characterize the dynamics of colonization, which increases early in patients who develop invasive candidiasis.

Thirteen years of surgical site infection surveillance in Swiss hospitals.

BACKGROUND: Surveillance is an essential element of surgical site infection (SSI) prevention. Few studies have evaluated the long-term effect of these programmes. AIM: To present data from a 13-year multicentre SSI surveillance programme from western and southern Switzerland. METHODS: Surveillance with post-discharge follow-up was performed according to the US National Nosocomial Infections Surveillance (NNIS) system methods. SSI rates were calculated for each surveyed type of surgery, overall and by year of participation in the programme. Risk factors for SSI and the effect of surveillance time on SSI rates were analysed by multiple logistic regression. FINDINGS: Overall SSI rates were 18.2% after 7411 colectomies, 6.4% after 6383 appendicectomies, 2.3% after 7411 cholecystectomies, 1.7% after 9933 herniorrhaphies, 1.6% after 6341 hip arthroplasties, and 1.3% after 3667 knee arthroplasties. The frequency of SSI detected after discharge varied between 21% for colectomy and 94% for knee arthroplasty. Independent risk factors for SSI differed between operations. The NNIS risk index was predictive of SSI in gastrointestinal surgery only. Laparoscopic technique was protective overall, but associated with higher rates of organ-space infections after appendicectomy. The duration of participation in the surveillance programme was not associated with a decreased SSI rate for any of the included procedure. CONCLUSION: These data confirm the effect of post-discharge surveillance on SSI rates and the protective effect of laparoscopy. There is a need to establish alternative case-mix adjustment methods. In contrast to other European programmes, no positive impact of surveillance duration on SSI rates was observed.

Thirteen years of surgical site infection surveillance in Swiss hospitals

Contexte : Les infections du site opératoire (Surgical Site Infections - SSI) sont des complications fréquentes des procédures chirurgicales et un problème majeur de la santé publique. La surveillance constitue un élément essentiel de la prévention des SSI. Les résultats publiés récemment par certains pays européens suggèrent un impact positif qu'un réseau de surveillance active peut avoir sur le taux de SSI dans les hôpitaux participants. Objectif : La présente étude évalue les effets de la surveillance sur l'incidence des SSI en analysant les résultats du programme suisse multicentrique de surveillance des SSI. Méthodes : L'étude porte sur les 13 premières années du programme, regroupant au total 23 hôpitaux périphériques, cantonaux et universitaires de la Suisse occidentale et du sud. Ce programme, qui a intégré le consortium national Swissnoso en 2011, a été organisé conformément aux principes du système américain de National Nosocomial Infections Surveillance (NNIS). La surveillance incluait les procédures de la chirurgie viscérale (appendicectomie, cholécystectomie, chirurgie du colon et herniaire) et de l'orthopédie (arthroplastie de la hanche et du genou). Les données démographiques et cliniques étaient recueillies de manière standardisée par les infirmières cliniciennes en infectiologie pendant et après l'hospitalisation. Les rapports annuels, résumant les taux des SSI pour chaque type de procédure ainsi que la comparaison inter-hospitalière des risques relatifs ajustés à l'index NNIS, ont été discutés au sein de chaque établissement entre le comité des chirurgiens et le responsable local du programme. Analyses statistiques : Les taux cumulatifs des SSI ont été calculés pour chaque procédure chirurgicale. Une stratification selon le type de SSI (superficielle, profonde, organe/espace) et selon l'index NNIS a été respectée. Les facteurs de risque des SSI ont été identifiés pour chaque procédure par les analyses univariées des caractéristiques du patient (âge, sexe, score ASA, temps avant l'opération) et celles de l'opération (classe de contamination, durée de la chirurgie, urgence, antibioprophylaxie, laparoscopie, procédures multiples, ré¬intervention). Afin d'évaluer l'effet de la durée de la surveillance sur le taux des SSI, le temps de participation au programme a été calculé et stratifié par périodes d'un an par hôpital et par procédure. La corrélation entre la durée de la surveillance et les SSI a été estimée en utilisant les modèles de régression logistique pour chaque procédure avec l'ajustement pour les variables avec p ^ 0.2. Dans toutes les analyses, la valeur p < 0.05 était considéré significative. Résultats : Les taux globaux des SSI étaient : 18.2% pour les colectomies, 6.4% pour les appendicectomies, 2.3% pour les cholécystectomies, 1.7% pour les cures des hernies et 1.6% et 1.3% pour les arthroplasties de la hanche et du genou, respectivement. L'incidence des SSI post-hospitalières allait du 21% pour les colectomies au 94% pour les arthroplasties du genou. Concernant les facteurs prédictifs des SSI, l'index NNIS était valable seulement pour la chirurgie gastro-intestinale, la laparoscopie étant globalement protectrice mais associée à un taux d'infections profondes plus élevé après l'appendicectomie. La durée de la participation au programme de surveillance n'apportait pas de diminution des taux des SSI dans aucune procédure incluse dans l'étude. Conclusions : L'étude confirme l'impact de la surveillance post-hospitalière sur le taux des SSI, l'effet protectrice de la laparoscopie ainsi que l'absence de la valeur prédictive de l'index NNIS en orthopédie. Contrairement aux autres programmes européens nous n'avons pas détecté d'effet positif de la durée de la surveillance sur le taux des SSI. Les résultats obtenus ouvrent la discussion sur l'utilisation plus effective des données de surveillance des SSI.

Polymorphisms in tumor necrosis factor-α increase susceptibility to intra-abdominal Candida infection in high-risk surgical ICU patients*.

OBJECTIVES: To evaluate the influence of genetic polymorphisms on the susceptibility to Candida colonization and intra-abdominal candidiasis, a blood culture-negative life-threatening infection in high-risk surgical ICU patients. DESIGN: Prospective observational cohort study. SETTING: Surgical ICUs from two University hospitals of the Fungal Infection Network of Switzerland. PATIENTS: Eighty-nine patients at high risk for intra-abdominal candidiasis (68 with recurrent gastrointestinal perforation and 21 with acute necrotizing pancreatitis). MEASUREMENTS AND MAIN RESULTS: Eighteen single-nucleotide polymorphisms in 16 genes previously associated with development of fungal infections were analyzed from patient's DNA by using an Illumina Veracode genotyping platform. Candida colonization was defined by recovery of Candida species from at least one nonsterile site by twice weekly monitoring of cultures from oropharynx, stools, urine, skin, and/or respiratory tract. A corrected colonization index greater than or equal to 0.4 defined "heavy" colonization. Intra-abdominal candidiasis was defined by the presence of clinical symptoms and signs of peritonitis or intra-abdominal abscess and isolation of Candida species either in pure or mixed culture from intraoperatively collected abdominal samples. Single-nucleotide polymorphisms in three innate immune genes were associated with development of a Candida corrected colonization index greater than or equal to 0.4 (Toll-like receptor rs4986790, hazard ratio = 3.39; 95% CI, 1.45-7.93; p = 0.005) or occurrence of intra-abdominal candidiasis (tumor necrosis factor-α rs1800629, hazard ratio = 4.31; 95% CI, 1.85-10.1; p= 0.0007; β-defensin 1 rs1800972, hazard ratio = 3.21; 95% CI, 1.36-7.59; p = 0.008). CONCLUSION: We report a strong association between the promoter rs1800629 single-nucleotide polymorphism in tumor necrosis factor-α and an increased susceptibility to intra-abdominal candidiasis in a homogenous prospective cohort of high-risk surgical ICU patients. This finding highlights the relevance of the tumor necrosis factor-α functional polymorphism in immune response to fungal pathogens. Immunogenetic profiling in patients at clinical high risk followed by targeted antifungal interventions may improve the prevention or preemptive management of this life-threatening infection.

Arginase activity in the blood of patients with visceral leishmaniasis and HIV infection.

BACKGROUND: Visceral leishmaniasis is a parasitic disease associated with high mortality. The most important foci of visceral leishmaniasis in Ethiopia are in the Northwest and are predominantly associated with high rates of HIV co-infection. Co-infection of visceral leishmaniasis patients with HIV results in higher mortality, treatment failure and relapse. We have previously shown that arginase, an enzyme associated with immunosuppression, was increased in patients with visceral leishmaniasis and in HIV seropositive patients; further our results showed that high arginase activity is a marker of disease severity. Here, we tested the hypothesis that increased arginase activities associated with visceral leishmaniasis and HIV infections synergize in patients co-infected with both pathogens. METHODOLOGY/PRINCIPAL FINDINGS: We recruited a cohort of patients with visceral leishmaniasis and a cohort of patients with visceral leishmaniasis and HIV infection from Gondar, Northwest Ethiopia, and recorded and compared their clinical data. Further, we measured the levels of arginase activity in the blood of these patients and identified the phenotype of arginase-expressing cells. Our results show that CD4(+) T cell counts were significantly lower and the parasite load in the spleen was significantly higher in co-infected patients. Moreover, our results demonstrate that arginase activity was significantly higher in peripheral blood mononuclear cells and plasma of co-infected patients. Finally, we identified the cells-expressing arginase in the PBMCs as low-density granulocytes. CONCLUSION: Our results suggest that increased arginase might contribute to the poor disease outcome characteristic of patients with visceral leishmaniasis and HIV co-infection.

Host- rather than virus-related factors reduce health-related quality of life in hepatitis C virus infection.

BACKGROUND: Hepatitis C virus (HCV) infection is associated with decreased health-related quality of life (HRQOL). Although HCV has been suggested to directly impair neuropsychiatric functions, other factors may also play a role. PATIENTS AND METHODS: In this cross-sectional study, we assessed the impact of various host-, disease- and virus-related factors on HRQOL in a large, unselected population of anti-HCV-positive subjects. All individuals (n = 1736) enrolled in the Swiss Hepatitis C Cohort Study (SCCS) were asked to complete the Short Form 36 (SF-36) and the Hospital Anxiety Depression Scale (HADS). RESULTS: 833 patients (48%) returned the questionnaires. Survey participants had significantly worse scores in both assessment instruments when compared to a general population. By multivariable analysis, reduced HRQOL (mental and physical summary scores of SF-36) was independently associated with income. In addition, a low physical summary score was associated with age and diabetes, whereas a low mental summary score was associated with intravenous drug use. HADS anxiety and depression scores were independently associated with income and intravenous drug use. In addition, HADS depression score was associated with diabetes. None of the SF-36 or HADS scores correlated with either the presence or the level of serum HCV RNA. In particular, SF-36 and HADS scores were comparable in 555 HCV RNA-positive and 262 HCV RNA-negative individuals. CONCLUSIONS: Anti-HCV-positive subjects have decreased HRQOL compared to controls. The magnitude of this decrease was clinically important for the SF-36 vitality score. Host and environmental, rather than viral factors, seem to impact on HRQOL level.

Incidence and risk factors for chronic elevation of alanine aminotransferase levels in HIV-infected persons without hepatitis b or c virus co-infection.

BACKGROUND: Chronic liver disease in human immunodeficiency virus (HIV)-infected patients is mostly caused by hepatitis virus co-infection. Other reasons for chronic alanine aminotransferase (ALT) elevation are more difficult to diagnose. METHODS: We studied the incidence of and risk factors for chronic elevation of ALT levels (greater than the upper limit of normal at 2 consecutive semi-annual visits) in participants of the Swiss HIV Cohort Study without hepatitis B virus (HBV) or hepatitis C virus (HCV) infection who were seen during the period 2002-2008. Poisson regression analysis was used. RESULTS: A total of 2365 participants were followed up for 9972 person-years (median age, 38 years; male sex, 66%; median CD4+ cell count, 426/microL; receipt of antiretroviral therapy [ART], 56%). A total of 385 participants (16%) developed chronic elevated ALT levels, with an incidence of 3.9 cases per 100 person-years (95% confidence interval [CI], 3.5-4.3 cases per 100 person-years). In multivariable analysis, chronic elevated ALT levels were associated with HIV RNA level >100,000 copies/mL (incidence rate ratio [IRR], 2.23; 95% CI, 1.45-3.43), increased body mass index (BMI, defined as weight in kilograms divided by the square of height in meters) (BMI of 25-29.9 was associated with an IRR of 1.56 [95% CI, 1.24-1.96]; a BMI 30 was associated with an IRR of 1.70 [95% CI, 1.16-2.51]), severe alcohol use (1.83 [1.19-2.80]), exposure to stavudine (IRR per year exposure, 1.12 [95% CI, 1.07-1.17]) and zidovudine (IRR per years of exposure, 1.04 [95% CI, 1.00-1.08]). Associations with cumulative exposure to combination ART, nucleoside reverse-transcriptase inhibitors, and unboosted protease inhibitors did not remain statistically significant after adjustment for exposure to stavudine. Black ethnicity was inversely correlated (IRR, 0.52 [95% CI, 0.33-0.82]). Treatment outcome and mortality did not differ between groups with and groups without elevated ALT levels. CONCLUSIONS: Among patients without hepatitis virus co-infection, the incidence of chronic elevated ALT levels was 3.9 cases per 100 person-years, which was associated with high HIV RNA levels, increased BMI, severe alcohol use, and prolonged stavudine and zidovudine exposure. Long-term follow-up is needed to assess whether chronic elevation of ALT levels will result in increased morbidity or mortality.