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BackgroundPre-existing lower urinary tract symptoms (LUTS), cognitive impairment, and the high prevalence of asymptomatic bacteriuria (ASB) complicate the diagnosis of urinary tract infection (UTI) in older women. The presence of pyuria remains the cornerstone of UTI diagnosis. However, >90% of ASB patients have pyuria, prompting unnecessary treatment. We quantified pyuria by automated microscopy and flowcytometry to determine the diagnostic accuracy for UTI and to derive pyuria thresholds for UTI in older women.MethodsWomen ≥65 years with ≥2 new-onset LUTS and 1 uropathogen ≥104 colony-forming units (CFU)/mL were included in the UTI group. Controls were asymptomatic and classified as ASB (1 uropathogen ≥105 CFU/mL), negative culture, or mixed flora. Patients with an indwelling catheter or antimicrobial pretreatment were excluded. Leukocyte medians were compared and sensitivity–specificity pairs were derived from a receiver operating characteristic curve.ResultsWe included 164 participants. UTI patients had higher median urinary leukocytes compared with control patients (microscopy: 900 vs 26 leukocytes/µL; flowcytometry: 1575 vs 23 leukocytes/µL; P < .001). Area under the curve was 0.93 for both methods. At a cutoff of 264 leukocytes/µL, sensitivity and specificity of microscopy were 88% (positive and negative likelihood ratio: 7.2 and 0.1, respectively). The commonly used cutoff of 10 leukocytes/µL had a poor specificity (36%) and a sensitivity of 100%.ConclusionsThe degree of pyuria can help to distinguish UTI in older women from ASB and asymptomatic controls with pyuria. Current pyuria cutoffs are too low and promote inappropriate UTI diagnosis in older women.Clinical trials registration. International Clinical Trials Registry Platform: NL9477 (https://trialsearch.who.int/Trial2.aspx?TrialID=NL9477)

The Dutch ‘search and destroy’ policy consists of screening patients with an increased risk of methicillin-resistant Staphylococcus aureus (MRSA) carriership and subsequent decolonization treatment when carriership is found. Decolonization therapy of individual MRSA carriers is effective. However, the effectiveness of the national ‘search and destroy’ policy is dependent on the entire cascade of care, including identification, referral, and subsequent treatment initiation in MRSA carriers. The aim of this study was to evaluate the leakages in the cascade of MRSA decolonization care. We assessed familiarity with the ‘search and destroy’ policy and the barriers in the uptake of MRSA eradication care using a questionnaire among 114 Dutch general practitioners. The main reasons for treatment were planned hospital visits, occupational reasons, and infections. The main reasons for refraining from eradication treatment were unfamiliarity with the ‘search and destroy’ policy and the assumption that MRSA carriership is often self-limiting. To optimize the continuity of the cascade of care, interventions should be aimed at supporting general practitioners and facilitating treatment and referral.

Acute kidney injury (AKI) is a frequent complication in patients with Staphylococcus aureus bacteremia (SAB), with a significant impact on patient management and outcome. This study aimed to provide insight in the proportion of patients with SAB that develop AKI, the risk factors for developing AKI in this population, and its reversibility. In this retrospective, multicenter cohort study, adult patients with SAB were eligible for inclusion. Patient characteristics, clinical variables, and laboratory results were retrieved from the electronic patient files. Primary outcome was development of AKI, defined as 1.5 times baseline creatinine. Secondary outcomes were reversibility of AKI and risk factors for AKI. A total of 315 patients with SAB were included, of whom 115/315 (37%) developed acute kidney injury. In 68/115 (59%), the AKI was reversible. If kidney function recovered, this occurred within 7 days in 56/68 (82%) of patients. In multivariable logistic regression analyses, independent risk factors for AKI were as follows: complicated SAB, use of diuretics, and hemodynamic instability. Development of AKI was associated with 30-day mortality (OR 3.9; CI 2.2-6.9; p < 0.01). Acute kidney injury is a frequent complication in patients with Staphylococcus aureus bacteremia. Considering the irreversibility in a relevant proportion of patients, future research into the underlying pathophysiology and potential interventions is warranted.

A significant proportion of the in-hospital antimicrobial consumption is used in the empiric setting, making empiric therapy an important target of stewardship interventions.Empiric antimicrobial therapy is the antimicrobial regimen that is started when the definite clinical diagnosis, causative agent and/or resistance pattern are yet unknown. Empiric therapy is accompanied by a varying level of uncertainty. In daily clinical practice, this uncertainty about the source, pathogen and susceptibility pattern are often managed by prescribing relatively broad-spectrum antimicrobial therapy. This has potential negative effects, such as toxicity and selective pressure resulting in antimicrobial resistance. Balancing the potential benefits and drawbacks of more broad-spectrum therapy is a substantial challenge, in particular when the level of uncertainty is high.This thesis aims to address the uncertainties most relevant in daily clinical practice in empiric antimicrobial therapy, to determine how they affect daily decision making, and to explore how this can be translated in antimicrobial policy making and antimicrobial stewardship.