Cees van Nieuwkoop

• MD, PhD
• Internist-Infectious Diseases Specialist at Haga Teaching Hospital

A 30-year-old man presented with community-acquired pneumonia (CAP), directly following influenza. Sputum Gram stain confirmed Staphylococcus aureus pneumonia. Initial empirical antimicrobial therapy did not cover S. aureus. The isolated S. aureus strain contained genes encoding exotoxins, such as Panton-Valentine leukocidin (PVL). This exotoxin is...

Lymphogranuloma venereum (LGV) is a sexually transmitted disease caused by Chlamydia trachomatis serovars L1 to L3. At present there is an epidemic of LGV proctitis in the Western world among men who have sex with men. HIV seropositivity and other sexual transmitted infections are the main risk factors.1 Moreover, a concurrent HIV infection seems t...

A capillary electrophoresis-time of flight-mass spectrometry (CE-TOF-MS) method for the analysis of amino acids in human urine was developed. Capillaries noncovalently coated with a bilayer of Polybrene (PB) and poly(vinyl sulfonate) (PVS) provided a considerable EOF at low pH, thus facilitating the fast separation of amino acids using a BGE of 1 M...

Background To prevent severe disease, nirmatrelvir/ritonavir (nirmatrelvir/r) is administered to individuals infected with SARS-CoV-2 who are at high risk, and it is currently priced at approximately $1375 in the Netherlands. We aim to evaluate the health outcomes and cost-effectiveness of nirmatrelvir/r among patients with high risk of severe dise...

Background Health-related quality of life (HRQoL) data post-COVID-19 in patients with medical conditions associated with severe disease is lacking. Here, we assess the longitudinal impact of COVID-19 on HRQoL and employment status in high-risk individuals. Methods In a multicenter prospective cohort study, high-risk (non-)hospitalized SARS-CoV-2-i...

Background We previously proposed bacteremia prediction models that might save a quarter of blood cultures (BCs) while missing few bacteremia patients. In this study, we aimed to validate these models in the United States.Table 1:Discrimination, calibration, and clinical usefulness upon external validation for five bacteremia prediction models.Basi...

Background Asymptomatic bacteriuria (ASB) is the presence of bacteria in the urine of patients without symptoms of a urinary tract infection. Generally, treating ASB is not beneficial. Objective We aimed to reduce overtreatment of ASB in the emergency department (ED) through a multifaceted de-implementation strategy. Design A stepped-wedge cluste...

Background The clinical frailty scale (CFS) was used as a triage tool for medical decision making during the COVID-19 pandemic. The CFS has been posed as a suitable risk marker for in-hospital mortality in COVID-19 patients. We evaluated whether the CFS is associated with mortality 24 months after hospitalisation for COVID-19. Methods The COvid ME...

Many physicians and patients hold the (unconscious) belief that intravenous antibiotic therapy is superior to oral therapy. This belief is also reflected in guidelines, where increasing severity of infection often leads to the recommendation of intravenous options only. But is this belief justified, and where does it come from? Treating with oral a...

Introduction Older adults with acute functional decline may visit emergency departments (EDs) for medical support despite a lack of strict medical urgency. The introduction of transitional care teams (TCT) at the ED has shown promise in reducing avoidable admittances. However, the optimal composition and implementation of TCTs are still poorly defi...

Objective: To determine patients' perspectives on home monitoring at emergency department (ED) presentation and shortly after admission and compare these with their physicians' perspectives. Methods: Forty Dutch hospitals participated in this prospective flash mob study. Adult patients with acute medical conditions, treated by internal medicine spe...

Deep brain stimulation (DBS) is an advanced treatment in Parkinson’s disease. We describe a 71-year-old patient in whom the DBS got infected with Mycobacterium bovis shortly after intravesical BCG instillations as an adjuvant treatment of bladder cancer. The DBS internal pulse generator and extension wires had to be replaced, and the patient was tr...

Community-acquired Pneumonia (CAP) guidelines generally recommend to admit patients with moderate-to-severe CAP and start treatment with intravenous antibiotics. This study aims to explore the clinical outcomes of oral antibiotics in patients with moderate-to-severe CAP. We performed a nested cohort study of an observational study including all adu...

Background Long-acting (LA) injectable therapy with cabotegravir (CAB) and rilpivirine (RPV) is currently used as maintenance treatment for human immunodeficiency virus type 1, and has a low risk for virological failure (VF). Although the risk is low, the circumstances and impact of VF in the real-world setting merit further evaluation. Methods We...

Background Blood cultures are commonly used at emergency departments (EDs), while only 5-10% yields a relevant pathogen. We aimed to develop an automatable prediction model in ED patients with suspected bacteremia. This may reduce the use of blood cultures and prevent potential harm from false-positive blood cultures, while minimizing the risk of m...

Remdesivir is a registered treatment for hospitalised patients with COVID-19 that has moderate clinical effectiveness. Anecdotally, some patients’ respiratory insufficiency seemed to recover particularly rapidly after initiation of remdesivir. In this study, we investigated if this rapid improvement was caused by remdesivir, and which patient chara...

Introduction: Older adults with an acute moderate-to-severe lower respiratory tract infection (LRTI) or pneumonia are generally treated in hospitals causing risk of iatrogenic harm such as functional decline and delirium. These hospitalisations are often a consequence of poor collaboration between regional care partners, the lack of (acute) diagno...

Defining urinary tract infection (UTI) is complex, as numerous clinical and diagnostic parameters are involved. In this systematic review we aimed to gain insight into how UTI is defined across current studies. We included 47 studies, published between January 2019 and May 2022, investigating therapeutic or prophylactic interventions in adult patie...

Introduction: Acute respiratory infections are common in frail, community-dwelling older people and are accompanied by considerable diagnostic and prognostic uncertainties. Inadequately coordinated care is associated with unnecessary hospital referral and admission with potential iatrogenic harm. Therefore, we aimed to co-create a regional integra...

Background and objectives: Posaconazole is used as prophylaxis of invasive fungal disease in immune-compromised haematological patients with prolonged neutropenia after intensive chemotherapy. During routine therapeutic drug monitoring of posaconazole, we repeatedly observed low posaconazole serum concentrations in patients that were concomitantly...

Background Recurrent urinary tract infections (UTIs) are common, especially in women. When oral antimicrobial prophylaxis is ineffective or not possible due to allergies or antimicrobial resistance, intravesical aminoglycoside instillations (IAIs) are a non-systemic alternative. Objectives To assess treatment satisfaction, long-term safety and eff...

Background The Pneumonia Severity Index (PSI) and the CURB-65 score assess disease severity in patients with community acquired pneumonia (CAP). We compared the clinical performance of both prognostic scores according to clinical outcomes and admission rates. Methods A nationwide retrospective cohort study was conducted using claims data from adul...

Background Pre-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, over 90% of ASB patients have pyuria, prompting unnecessary tr...

Objectives: To test whether BCG vaccination would reduce the incidence of COVID-19 and other respiratory tract infections in older adults with one or more comorbidities. Methods: Community-dwelling adults over 60 years old with one or more underlying comorbidities and no contra-indications for BCG vaccination were randomized 1:1 to BCG or placeb...

The optimal drug of choice, its time of administration and duration of antibiotic prophylaxis in patient undergoing a TURP procedure are still matters of debate. In this study, we evaluated the concentrations of cefazolin, ciprofloxacin and fosfomycin in the human prostate in a cohort of men undergoing TURP. We compared prostate tissue concentratio...

Background The Pneumonia Severity Index (PSI) and the Confusion, Urea nitrogen, Respiratory rate, Blood pressure, 65 years of age and older (CURB-65) score can assess the severity in patients with community acquired pneumonia (CAP). We compared the clinical performance of both prognostic scores according to clinical outcome and admission rates. Me...

Background: Timely identification of deteriorating COVID-19 patients is needed to guide changes in clinical management and admission to intensive care units (ICUs). There is significant concern that widely used Early warning scores (EWSs) underesti- mate illness severity in COVID-19 patients and therefore, we developed an early warn- ing model spec...

Importance: Misdiagnosis of infection is among the most commonly made diagnostic errors and is associated with increased morbidity and mortality. Little is known about how often misdiagnosed site of infection occurs and its association with clinical outcomes. Objectives: To evaluate the discrepancy between admission and discharge site of infecti...

Accumulating evidence from randomized controlled trials (RCTs) supports 7 days treatment for uncomplicated Gram-negative bacteraemia. However, some patient populations were not well represented in these RCTs, including critically ill patients, immunocompromised patients and those with MDR bacteria. In this debate document, we discuss the pros and c...

The objective of this study was to describe the population pharmacokinetics of remdesivir and GS-441524 in hospitalized coronavirus disease 2019 (COVID-19) patients. A prospective observational pharmacokinetic study was performed in non-critically ill hospitalized COVID-19 patients with hypoxemia. For evaluation of the plasma concentrations of remd...

Objectives The COVID-19 pandemic increases healthcare worker (HCW) absenteeism. The Bacillus Calmette-Guérin (BCG) vaccine may provide non-specific protection against respiratory infections through enhancement of trained immunity. We investigated the impact of BCG vaccination on HCW absenteeism during the COVID-19 pandemic. Methods HCWs exposed to...

Background: Timely identification of deteriorating COVID-19 patients is needed to guide changes in clinical management and admission to intensive care units (ICUs). There is significant concern that widely used early warning scores (EWSs) underestimate illness severity in COVID-19 patients and therefore, we developed an early warning model specific...

We discovered a highly virulent variant of subtype-B HIV-1 in the Netherlands. One hundred nine individuals with this variant had a 0.54 to 0.74 log10 increase (i.e., a ~3.5-fold to 5.5-fold increase) in viral load compared with, and exhibited CD4 cell decline twice as fast as, 6604 individuals with other subtype-B strains. Without treatment, advan...

Introduction Hypokalaemia is a potentially life‐threatening adverse event of flucloxacillin with unknown incidence. The risk of flucloxacillin‐induced hypokalaemia has recently been suggested to be increased among females compared to males. The aim of this study is to describe the incidence and to determine the influence of sex and other risk facto...

Chronic bacterial prostatitis is increasingly difficult to treat due to rising antimicrobial resistance limiting oral treatment options. In this case series, 11 men with CBP (including patients with urological comorbidities) due to multi-resistant E. coli were treated with once-daily ceftriaxone intravenously for 6 weeks. Nine patients were clinica...

Background: The severity of COVID-19 after SARS-CoV-2 infection is unpredictable. Angiotensin-converting enzyme-2 (ACE2) is the receptor responsible for coronavirus binding, while subsequent cell entry relies on priming by the serine protease TMPRSS2 (transmembrane protease, serine 2). Although renin-angiotensin-aldosterone-system (RAAS) blockers...

Background We aimed to determine the non-inferiority of fosfomycin, compared to ciprofloxacin, as oral stepdown treatment for E. coli febrile urinary tract infections (fUTIs) in women. Methods This was a double-blind, randomised controlled trial in 15 Dutch hospitals. Adult women receiving 2-5 days of empirical intravenous antimicrobials for E.col...

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Background: Guidelines recommend maximal efforts to obtain blood and sputum cultures in patients with COVID-19, as bacterial coinfection is associated with worse outcomes. The aim of this study was to evaluate the yield of bacteriological tests, including blood and sputum cultures, and the association of multiple biomarkers and the Pneumonia Sever...

Background The severity of COVID-19 after SARS-CoV-2 infection is unpredictable. Angiotensin-converting enzyme-2 (ACE2) is the receptor responsible for coronavirus binding, while subsequent cell entry relies on priming by the serine protease TMPRSS2 (transmembrane protease, serine 2). Although renin-angiotensin-aldosterone-system (RAAS) blockers ha...

Background: Various metrics of hospital antibiotic use might assist in guiding antimicrobial stewardship (AMS). Objectives: To compare patient outcomes in association with three methods to measure and feedback information on hospital antibiotic use when used in developing an AMS intervention. Methods: Three methods were randomly allocated to 4...

Introduction Antimicrobial treatment of asymptomatic bacteriuria (ASB) is one of the most common unnecessary uses of antimicrobials. Earlier studies have shown that the prevalence of this inappropriate treatment ranges from 45% to 83%. Multifaceted interventions based on international guidelines and antimicrobial stewardship can decrease overtreatm...

Background: During the COVID-19 pandemic, the scarcity of resources has necessitated triage of critical care for patients with the disease. In patients aged 65 years and older, triage decisions are regularly based on degree of frailty measured by the Clinical Frailty Scale (CFS). However, the CFS could also be useful in patients younger than 65 ye...

Background The majority of HCV infections are found in low- and middle-income countries, harboring many region-specific HCV subtypes. Nevertheless, direct-acting antivirals (DAA) trials were almost exclusively conducted in high-income countries, where mainly epidemically spread HCV subtypes are present. Recently, several studies demonstrated sub-op...

Introduction The addition of the β-lactamase inhibitor relebactam to imipenem restores the antibacterial activity against the majority of multidrug resistant Gram-negative bacteria. Complicated urinary tract infections (UTIs) are predominantly caused by Gram-negative uropathogens. The rise in antibiotic resistance, including to carbapenems, is an i...

Objectives: To evaluate the pharmacokinetics and clinical effectiveness of IV and oral fosfomycin treatment in patients with recurrent urinary tract infection (rUTI) with Escherichia coli. Patients and methods: Patients with rUTI treated with 3 g of oral fosfomycin every 72 h for at least 14 days were included in a prospective open-label single-...

We report a case of a male with COVID-19 who developed acute hepatotoxicity related to remdesivir with probable interaction of P-glycoprotein (P-gp) inhibitors. Until further details upon this interaction become available, we recommend physicians to be cautious with the prescription of P-gp inhibitors in patients receiving remdesivir therapy.

Chloroquine and hydroxychloroquine are both used to treat COVID-19. Safety data in this specific population is largely unknown. In particular, cardiologic, gastro-intestinal and neuropsychiatric side-effects of (hydroxychloroquine) needs special attention in COVID-19 patients.

Abstract Background A reduction in duration of antibiotic therapy is crucial in minimizing the development of antimicrobial resistance, drug-related side effects and health care costs. The minimal effective duration of antimicrobial therapy for febrile urinary tract infections (fUTI) remains a topic of uncertainty, especially in male patients, thos...

Patient: Male, 47 Final Diagnosis: Acute renal and splenic infarction Symptoms: Flank pain • low-grade fever Medication: — Clinical Procedure: CT scan Specialty: Nephrology Objective Challenging differential diagnosis Background This is a case report of a male patient who presented with a history of right flank pain based on renal infarction. Ini...

Background Febrile Urinary Tract Infection (FUTI) is frequently treated initially with intravenous antibiotics, followed by oral antibiotics guided by clinical response and bacterial susceptibility patterns. Due to increasing infection rates with multiresistant Enterobacteriaceae, antibiotic options for stepdown treatment decline and patients more...

Background There is increasing interest in outpatient parenteral antimicrobial treatment. Objective To evaluate the added value of consultation of an infectious diseases expert team (consisting of two internist-infectious diseases specialists and a microbiologist) for advice regarding type, administration route and duration of antibiotic treatment....

Purpose: Antimicrobial resistance leads to complications in the management of recurrent urinary tract infections. In some patients with recurrent urinary tract infections who have limited treatment options intravenous therapy with reserve antibiotics is often required. In this study we assessed the effectiveness, safety and feasibility of prophyla...

Background: Several promising human immunodeficiency virus (HIV) treatment adherence interventions have been identified, but data about their cost-effectiveness are lacking. This study examines the trial-based cost-effectiveness and cost-utility of the proven-effective Adherence Improving Self-Management Strategy (AIMS), from a societal perspectiv...

Lyme disease (LD) is the most common tick-borne illness. The diagnosis of LD is difficult because of the great variation in clinical manifestations. Although abdominal pain is generally not considered a sign of LD, in this case report we describe a patient with unexplained severe abdominal pain that eventually turned out to be LD due to radiculopat...

Objectives: Febrile urinary tract infections (fUTI) can often be treated safely with oral antimicrobials in an outpatient setting. However, a minority of patients develop complications that may progress into septic shock. An accurate assessment of disease severity upon emergency department (ED) presentation is therefore crucial in order to guide t...

Fosfomycin has emerged as a potential therapy for multidrug-resistant bacterial infections. In most European countries, the oral formulation is only approved as a 3 g single dose for treatment of uncomplicated cystitis. However, for the treatment of complicated systemic infections, this dose regimen is unlikely to reach efficacious serum and tissue...

Fosfomycin is a bactericidal, low-molecular weight, broad-spectrum antibiotic, with putative activity against several bacteria, including multidrug-resistant Gram-negative bacteria, by irreversibly inhibiting an early stage in cell wall synthesis. Evidence suggests that fosfomycin has a synergistic effect when used in combination with other antimic...

Abstract Background There is a lack of severity assessment tools to identify adults presenting with febrile urinary tract infection (FUTI) at risk for complicated outcome and guide admission policy. We aimed to validate the Prediction Rule for Admission policy in Complicated urinary Tract InfeCtion LEiden (PRACTICE), a modified form of the pneumoni...

Background In adults with febrile urinary tract infection (fUTI), data on optimal treatment duration in patients other than non-pregnant women without comorbidities are lacking. MethodsA randomized placebo-controlled, double-blind, non-inferiority trial among 35 primary care centers and 7 emergency departments of regional hospitals in the Netherlan...

Background: No high-quality trials have provided evidence of effectiveness and cost-effectiveness of HIV treatment adherence intervention strategies. We therefore examined the effectiveness and cost-effectiveness of the Adherence Improving self-Management Strategy (AIMS) compared with treatment as usual. Methods: We did a pragmatic, multicentre,...

Clioquinol is used for treatment of amoebiasis and infection with Dientamoeba fragilis. In a guideline of the Dutch Working Party on Antibiotic Policy, clioquinol is recommended as a first-choice treatment for Dientamoeba fragilis. This drug, however, is associated with subacute myelo-optico-neuropathy (SMON). It was withdrawn from the market world...

- Fosfomycin is a broad-spectrum antibiotic agent used orally for uncomplicated cystitis. The intravenous form of administration has recently been authorised in the Netherlands.- Thanks to its broad spectrum and extensive tissue penetration, fosfomycin offers possibilities for the treatment of infections in different organs.- Infections with multid...

- Fosfomycin is a broad-spectrum antibiotic agent used orally for uncomplicated cystitis. The intravenous form of administration has recently been authorised in the Netherlands.- Thanks to its broad spectrum and extensive tissue penetration, fosfomycin offers possibilities for the treatment of infections in different organs.- Infections with multid...

Background: Several infectious processes of intra-abdominal origin may atypically present as skin or soft tissue infections or abscess in the thigh. Case report: We describe the case of a 73-year-old woman who presented to the emergency department with the clinical picture of a skin infection of the right leg. The patient's condition deteriorate...

The association between combination antiretroviral therapy (cART) and cancer risk, especially regimens containing protease inhibitors (PIs) or nonnucleoside reverse transcriptase inhibitors (NNRTIs), is unclear. Participants were followed from the latest of D:A:D study entry or January 1, 2004, until the earliest of a first cancer diagnosis, Februa...

Objective/purpose: Febrile urinary tract infection (UTI) is a common bacterial disease that may lead to substantial morbidity and mortality especially among the elderly. Little is known about biomarkers that predict a complicated course. Our aim was to determine the role of certain urinary cytokines or antimicrobial proteins, plasma vitamin D leve...

Background: Chronic kidney disease (CKD) is a major health issue for HIV-positive individuals, associated with increased morbidity and mortality. Development and implementation of a risk score model for CKD would allow comparison of the risks and benefits of adding potentially nephrotoxic antiretrovirals to a treatment regimen and would identify t...

We describe a case of a 44-year-old woman with a borderline personality disorder and chronic gamma- butyrolactone (GBL) use who presented with progressive dyspnoea and an altered mental status. A high anion gap metabolic acidosis and acute lung injury was diagnosed. We hypothesise this was caused by GBL. In this case report we describe the diagnost...

Colistin (polymyxin E) is a positively charged deca-peptide antibiotic that disrupts the integrity of the outer membrane of the cell wall of Gram-negative bacteria by binding to the lipid A moiety of lipopolysacharides (LPS), resulting in cell death. The endotoxic activity of LPS is simultaneously inhibited. Colistin is increasingly being prescribe...

Purpose of review: To review the recent advances in the diagnostic and therapeutic approach to adults presenting with febrile urinary tract infection (UTI) in the emergency department (ED). Recent findings: Recent research suggests overdiagnosis and therefore overtreatment of UTI in the ED, especially in the elderly. Antimicrobial pretreatment,...

- Colistin (polymyxin E) binds to the cell wall of gram-negative bacteria, leading to osmotic destruction of the cell.- Since its introduction in 1959, colistin has been little used parenterally due to a high incidence of reversible nephrotoxicity and, to a lesser extent, neurotoxicity.- Colistin use remained limited to combating Pseudomonas aerugi...

Bacterial infections such as febrile urinary tract infection (fUTI) may run a complicated course which is difficult to foretell on clinical evaluation only. Because the conventional biomarkers erythrocyte sedimentation rate (ESR), leukocyte count, C-reactive protein (CRP) and procalcitonin (PCT) have a limited role in the prediction of a complicate...

The aim of the study was to statistically model the relative increased risk of cardiovascular disease (CVD) per year older in Data collection on Adverse events of anti-HIV Drugs (D:A:D) and to compare this with the relative increased risk of CVD per year older in general population risk equations. We analysed three endpoints: myocardial infarction...

No consensus exists on how to define abnormally rapid deterioration in renal function (Rapid Progression, RP). We developed an operational definition of RP in HIV-positive persons with baseline estimated glomerular filtration rate (eGFR) >90 ml/min/1.73 m2 (using Cockcroft Gault) in the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) st...

With the advent of effective antiretroviral treatment, the life expectancy for people with HIV is now approaching that seen in the general population. Consequently, the relative importance of other traditionally non-AIDS-related morbidities has increased. We investigated trends over time in all-cause mortality and for specific causes of death in pe...

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...

Background: In patients with multidrug-resistant (MDR) bacteria causing lower urinary tract infection (lUTI), intravesical gentamicin (iGM) installation is a potential treatment when other options are limited. Locally iGM precludes systemic toxicity and development of antimicrobial resistance is unlikely because of high urinary concentration and...

Urinary tract infection (UTI) encompasses a variety of clinical syndromes ranging from mild to life-threatening conditions. As such, it represents an interesting model for the development of an analytically based scoring system of disease severity and/or host response. Here we test the feasibility of this concept using 1H NMR based metabolomics as...