Jan W. van’t Wout

Procalcitonin reflects bacteremia and bacterial load in urosepsis syndrome: a prospective observational study

IntroductionGuidelines recommend that two blood cultures be performed in patients with febrile urinary tract infection (UTI), to detect bacteremia and help diagnose urosepsis. The usefulness and cost-effectiveness of this practice have been criticized. This study aimed to evaluate clinical characteristics and the biomarker procalcitonin (PCT) as an aid in predicting bacteremia.MethodsA prospective observational multicenter cohort study included consecutive adults with febrile UTI in 35 primary care units and 8 emergency departments of 7 regional hospitals. Clinical and microbiological data were collected and PCT and time to positivity (TTP) of blood culture were measured.ResultsOf 581 evaluable patients, 136 (23%) had bacteremia. The median age was 66 years (interquartile range 46 to 78 years) and 219 (38%) were male. We evaluated three different models: a clinical model including seven bed-side characteristics, the clinical model plus PCT, and a PCT only model. The diagnostic abilities of these models as reflected by area under the curve of the receiver operating characteristic were 0.71 (95% confidence interval (CI): 0.66 to 0.76), 0.79 (95% CI: 0.75 to 0.83) and 0.73 (95% CI: 0.68 to 0.77) respectively. Calculating corresponding sensitivity and specificity for the presence of bacteremia after each step of adding a significant predictor in the model yielded that the PCT > 0.25 μg/l only model had the best diagnostic performance (sensitivity 0.95; 95% CI: 0.89 to 0.98, specificity 0.50; 95% CI: 0.46 to 0.55). Using PCT as a single decision tool, this would result in 40% fewer blood cultures being taken, while still identifying 94 to 99% of patients with bacteremia.The TTP of E. coli positive blood cultures was linearly correlated with the PCT log value; the higher the PCT the shorter the TTP (R2 = 0.278, P = 0.007).ConclusionsPCT accurately predicts the presence of bacteremia and bacterial load in patients with febrile UTI. This may be a helpful biomarker to limit use of blood culture resources.

Risk factors for fluoroquinolone-resistant Escherichia coli in adults with community-onset febrile urinary tract infection

OBJECTIVES To assess risk factors for fluoroquinolone resistance in community-onset febrile Escherichia coli urinary tract infection (UTI). METHODS A nested case-control study within a cohort of consecutive adults with febrile UTI presenting at primary healthcare centres or emergency departments during January 2004 through December 2009. Resistance was defined using EUCAST criteria (ciprofloxacin MIC >1.0 mg/L). Cases were subjects with fluoroquinolone-resistant E. coli, and controls those with fluoroquinolone-susceptible isolates. Multivariable logistic regression analysis was used to identify potential risk factors for fluoroquinolone resistance. RESULTS Of 787 consecutive patients, 420 had E. coli-positive urine cultures. Of these, 51 (12%) were fluoroquinolone resistant. Independent risk factors for fluoroquinolone resistance were urinary catheter [odds ratio (OR) 3.1; 95% confidence interval (CI) 0.9-11.6], recent hospitalization (OR 2.0; 95% CI 1.0-4.3) and fluoroquinolone use in the past 6 months (OR 17.5; 95% CI 6.0-50.7). Environmental factors (e.g. contact with animals or hospitalized household members) were not associated with fluoroquinolone resistance. Of fluoroquinolone-resistant strains, 33% were resistant to amoxicillin/clavulanate and 65% to trimethoprim/sulfamethoxazole; 14% were extended-spectrum β-lactamase (ESBL) positive compared with <1% of fluoroquinolone-susceptible isolates. CONCLUSIONS Recent hospitalization, urinary catheter and fluoroquinolone use in the past 6 months were independent risk factors for fluoroquinolone resistance in community-onset febrile E. coli UTI. Contact with animals or hospitalized household members was not associated with fluoroquinolone resistance. Fluoroquinolone resistance may be a marker of broader resistance, including ESBL positivity.

Antimicrobial peptides: therapeutic potential for the treatment of Candida infections.

The increasing frequency of fungal infections in immunocompromised patients together with the emergence of strains resistant to currently used antifungal drugs point to an increased need for a new class of antimycotics. Antimicrobial peptides are promising candidates for the treatment of fungal infections since they have both mechanisms of action distinct from available antifungal agents and the ability to regulate the host immune defence systems as well. This review focuses on Candida albicans as a large amount of work on the mechanisms of action of classical antifungals as well as antimicrobial peptides, such as defensins, protegrins, histatins and lactoferrin (LF)-derived peptides, has been performed in this yeast. Analogues of these antimicrobial peptides and combinations of antimicrobial peptides with classical antimycotics are under investigation for treatment of candidiasis.

Risk Factors for Bacteremia with Uropathogen Not Cultured from Urine in Adults with Febrile Urinary Tract Infection

In a prospective study involving 642 patients with febrile urinary tract infection (UTI), we found antimicrobial pretreatment (odds ratio [OR], 3.3), an indwelling urinary catheter (OR, 2.8), and malignancy (OR, 2.7) to be independent risk factors for bacteremia with a uropathogen that was not cultured or recognized in the urine. Although the diagnostic value of blood cultures has been questioned in UTI, we advocate performing blood cultures for patients with these risk factors.

Implications of chills.

with bacteraemia, endotoxaemia, and cytokinaemia in a prospective study of 464 consecutive patients (median age 61; 272 men, 192 women) who came to hospital with fever. 90 (19%) had bacteraemia (42 gram-positive, 44 gramnegative, and four both). 33 patients (7·1%) died in hospital. In 399 (86%), fever was caused by infection, typically of the respiratory or urinary tracts; chills occurred in 146 (36·6%) of these compared with eight (12·3%) of 65 feverish patients without infection (p=0·001). Chills were more common in patients with gram-negative infection than gram-positive or viral infecton (44 vs 33%) (table). Patients with chills had higher plasma concentrations of TNF , IL-6, IL-10, and endotoxin compared with patients without chills (table). On admission, 16 of 154 (10·4%) patients with chills were in shock compared with 12 of 235 (5·1%) patients without ( , p=0·049). Bacteraemia (RR 2·50 [95% CI 1·5–4·1]) and endotoxaemia (RR 1·65 [1·0–2·7]) was more frequent in patients with chills. Age, sex, underlying disease (classified by McCabe-Jackson) and use of antibiotics or immunosuppressives did not differ between patients with chills and those without . In patients with bacteraemia, age did not significantly affect occurrence of chills, nor did duration of fever. The findings were validated in 113 febrile patients consecutively admitted to another hospital. In this set, chills were associated with bacteraemia (RR 4·3, [1·5–12]) but not outcome. Our data confirm clinical wisdom that chills are associated with micro-organisms in the blood. High concentrations of the pro-inflammatory cytokine TNF and bacteraemia are strongly associated with the chills. However, chills do not equate with bacteraemia: the sensitivity of chills was 58% and 73%, and specificity 65% and 62% in the two hospitals. Given the prevalence of bacteraemia of about 20% in febrile patients admitted with community-acquired infection, the negative predictive power of absence of chills is high—about 85%.

A case of rickettsialpox in Northern Europe

We report the first case of rickettsialpox caused by Rickettsia akari in the Netherlands. The diagnosis was suspected based on clinical grounds and was confirmed by Western blot analysis with cross-adsorption. Because the arthropod vector (Liponyssoides sanguineus) is ubiquitous, we suspect that the disease is under-diagnosed in non-endemic areas.

Diabetes and the Course of Febrile Urinary Tract Infection

Diabetes is considered a risk factor for acquisition of febrile urinary tract infection (UTI) (1,2), but there is a lack of information on the association of diabetes with the subsequent course of disease and its outcome. We performed a prospective observational multicenter cohort study including consecutive adults with community-onset febrile UTI presenting at 7 emergency departments and 35 primary care centers. The effect of preexisting diabetes on presentation and microbiological and clinical outcome was assessed and multivariable logistic regression performed to establish whether diabetes was an independent risk factor for a complicated course. View this table: Table 1 Baseline characteristics of 858 patients presenting with febrile UTI Of 858 patients, 140 had diabetes (93% type 2 diabetes), of whom 41 (30%) used insulin, 19 (14%) were managed by diet only, and the remaining were managed by a combination of metformin, insulin, and diet. Patients with diabetes were older (median age 73 years [interquartile range {IQR} 46–78] vs. 64 [IQR 42–77], P < 0.001), were more frequently male (48 vs. 35%, P = 0.006), and had a higher …