Duncan R Cranendonk

University of Amsterdam

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W. Joost Wiersinga

Amsterdam University Medical Centers

Tom van der Poll

Institute of Infection and Immunity

Jan M. Prins

University of Amsterdam

Marc J. M. Bonten

Utrecht University

Janneke Horn

University of Amsterdam

Lonneke A. van Vught

Amsterdam University Medical Centers

Maryse A. Wiewel

Academic Medical Center

Olaf L. Cremer

University Medical Center Utrecht

M. Nastou

G. Papanikolaou General Hospital

Carley N. Gemelli

Australian Red Cross Lifeblood

Cooperative Institutions

Inserm

University of Amsterdam

Academic Medical Center

Universidade de São Paulo

Amsterdam University Medical Centers

Assistance Publique – Hôpitaux de Paris

Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo

King Saud bin Abdulaziz University for Health Sciences

Intensive Care Society

University of Toronto

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Antibiotic treatment for 6 days versus 12 days in patients with severe cellulitis: a multicentre randomized, double-blind, placebo-controlled, non-inferiority trial

Clinical Microbiology and Infection (2019)

Duncan R Cranendonk Brent C. Opmeer Michiel A. van Agtmael Judith Branger K. Brinkman

10.1016/j.cmi.2019.09.019

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Citations (44)

Cellulitis: current insights into pathophysiology and clinical management.

PubMed (2017)

Duncan R Cranendonk A.P.M. Lavrijsen Jan M. Prins W. Joost Wiersinga

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Comparing short to standard duration of antibiotic therapy for patients hospitalized with cellulitis (DANCE): study protocol for a randomized controlled trial

BMC Infectious Diseases (2014)

Duncan R Cranendonk Brent C. Opmeer Jan M. Prins W. Joost Wiersinga

Recommended therapy duration for patients hospitalized with cellulitis is 10-14 days. Unnecessary use of antibiotics is one of the key factors driving resistance. Recent studies have shown that antibiotic therapy for cellulitis in outpatients can safely be shortened, despite residual inflammation. This study will compare in hospitalized patients the safety and effectiveness of shortening antibiotic therapy for cellulitis from 12 to 6 days.

Flucloxacillin

Erysipelas

Erythema

Cellulite

10.1186/1471-2334-14-235

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Citations (12)

The Skin Microbiota in Patients Hospitalized for Cellulitis and Association With Outcome

Clinical Infectious Diseases (2018)

Duncan R Cranendonk Floor Hugenholtz Jan M. Prins Paul H. M. Savelkoul Andries E. Budding

The skin microbiota plays a key role in the pathogenesis of several skin diseases, but its role in cellulitis remains unknown. We investigated the skin microbiota in patients with cellulitis, studied whether its analysis could help determine the causative pathogen, and explored whether skin microbiota composition was associated with clinical outcomes.We prospectively included 58 patients hospitalized for cellulitis. Skin swabs obtained from the lesion sites were compared with swabs from identical sites on the contralateral unaffected limbs and with swabs obtained from 19 age- and sex-matched control subjects without cellulitis. Bacterial profiling of the skin microbiota was performed by interspacer profiling (IS-pro).A large interpersonal variation in the skin microbiota composition of patients hospitalized with cellulitis was observed. Firmicutes were the dominant phylum, and Staphylococcus and Streptococcus the dominant genera. In most patients, a strong correlation between the microbiota of the affected lesion and the microbiota of the unaffected, contralateral limb was seen. Overall, the composition of the cellulitis microbiota could not be distinguished from the skin microbiota of controls. No consistent association could be found between traditional culture results and skin microbiota signatures in patients with cellulitis. Lastly, we found that neither microbiota composition nor diversity were associated with clinical parameters and outcomes in patients with cellulitis.In this exploratory study on the skin microbiota in patients hospitalized with cellulitis, we were unable to identify a typical cellulitis microbiota. The diagnostic and prognostic information that could be derived from skin microbiota profiling in this patient cohort was limited.NCT02032654.

10.1093/cid/ciy709

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Antibiotic-induced gut microbiota disruption during human endotoxemia: a randomised controlled study

Gut (2016)

Jacqueline M. Lankelma Duncan R Cranendonk Clara Belzer Alex F. de Vos Willem M. de Vos

Objective

The gut microbiota is essential for the development of the intestinal immune system. Animal models have suggested that the gut microbiota also acts as a major modulator of systemic innate immunity during sepsis. Microbiota disruption by broad-spectrum antibiotics could thus have adverse effects on cellular responsiveness towards invading pathogens. As such, the use of antibiotics may attribute to immunosuppression as seen in sepsis. We aimed to test whether disruption of the gut microbiota affects systemic innate immune responses during endotoxemia in healthy subjects.

Design

In this proof-of-principle intervention trial, 16 healthy young men received either no treatment or broad-spectrum antibiotics (ciprofloxacin, vancomycin and metronidazole) for 7 days, after which all were administered lipopolysaccharide intravenously to induce a transient sepsis-like syndrome. At various time points, blood and faeces were sampled.

Results

Gut microbiota diversity was significantly lowered by the antibiotic treatment in all subjects. Clinical parameters, neutrophil influx, cytokine production, coagulation activation and endothelial activation during endotoxemia were not different between antibiotic-pretreated and control individuals. Antibiotic treatment had no impact on blood leucocyte responsiveness to various Toll-like receptor ligands and clinically relevant causative agents of sepsis (Streptococcus pneumoniae, Klebsiella pneumoniae, Escherichia coli) during endotoxemia.

Conclusions

These findings suggest that gut microbiota disruption by broad-spectrum antibiotics does not affect systemic innate immune responses in healthy subjects during endotoxemia in humans, disproving our hypothesis. Further research is needed to test this hypothesis in critically ill patients. These data underline the importance of translating findings in mice to humans.

Trial registration number

ClinicalTrials.gov (NCT02127749; Pre-results).

10.1136/gutjnl-2016-312132

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‘Antibiotic treatment for 6 days versus 12 days in patients with severe cellulitis’ – Author's reply

Clinical Microbiology and Infection (2020)

Duncan R Cranendonk Jan M. Prins W. Joost Wiersinga

10.1016/j.cmi.2020.02.035

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Clinical Characteristics and Outcomes of Patients With Cellulitis Requiring Intensive Care

JAMA Dermatology (2017)

Duncan R Cranendonk Lonneke A. van Vught Maryse A. Wiewel Olaf L. Cremer Janneke Horn

Importance

Cellulitis is a commonly occurring skin and soft tissue infection and one of the most frequently seen dermatological diseases in the intensive care unit (ICU). However, clinical characteristics of patients with cellulitis requiring intensive care treatment are poorly defined. Necrotizing fasciitis is often confused for cellulitis at initial presentation and is considered to be more severe and thus has previously been described in more detail.

Objective

To describe the clinical presentation and outcomes of patients with ICU-necessitating cellulitis and to compare them with patients with necrotizing fasciitis.

Design, Setting, and Participants

This prospective cohort study includes all ICU admissions from 2 tertiary hospitals in the Netherlands. Of 2562 sepsis admissions, 101 had possible, probable, or definite cellulitis or soft tissue infections. Retrospective review identified severe cellulitis was the reason for ICU admission in 23 patients, necrotizing fasciitis in 31 patients, and other diagnoses in 47 patients.

Main Outcomes and Measures

Patient and disease characteristics, cultured pathogens, lengths of stay, and short-term and long-term mortality.

Results

Overall, 54 patients with cellulitis (n = 23; mean [SD] age, 57.2 [17.7] years) or necrotizing fasciitis (n = 31; mean [SD] age, 54.3 [13.5]) were included in this study. Patients with cellulitis were found to be less severely ill than patients with necrotizing fasciitis. This is reflected in rates of shock (7 [30.4%] vs 19 [61.3%];P = .03), need for mechanical ventilation (12 [52.2%] vs 19 [93.5%];P = .003) and slightly lower mean Sequential Organ Failure Assessment scores (8 vs 10;P = .046). Median (interquartile range [IQR]) Acute Physiology and Chronic Health Evaluation IV scores did not differ significantly (82 [75-98] vs 76 [70-96];P = .16). Patients with cellulitis had more chronic comorbidities than patients with necrotizing fasciitis (20 [87.0%] vs 17 [54.8%];P = .02), especially cardiovascular insufficiencies (10 [43.5%] vs 4 [12.9%];P = .02) and immunodeficiencies (9 [39.1%] vs 3 [9.7%];P = .02). Among patients with cellulitis and patients with patients with necrotizing fasciitis,Staphylococcus aureus(10 [43.5%] vs 4 [12.9%];P = .02),Streptococcus pyogenes(2 [8.7%] vs 19 [61.3%];P < .001) andEscherichia coli(4 [17.4%] vs 5 [16.2%];P = .90) were the most frequently observed pathogens. Median (IQR) length of ICU stay was shorter for patients with cellulitis vs patients with necrotizing fasciitis (3 [2-5] vs 5 [3-11];P = .01), while median (IQR) hospital length of stay did not differ significantly (22 [10.25-32] vs 36 [14.25-40];P = .16); and the in-hospital mortality rate (26.1% vs 22.6%,P > .99) and 90-day mortality rate (30.4% vs 22.6%;P = .54) were similar.

Conclusions and Relevance

Patients with cellulitis patients are seldom admitted to the ICU. However, while these patients are less critically ill on admission than patients with necrotizing fasciitis, they have more chronic comorbidities and most notably similar short-term and long-term mortality.

Trial Registration

clinicaltrials.gov Identifier:NCT01905033

Interquartile range

Cellulite

10.1001/jamadermatol.2017.0159

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Citations (24)

Erratum to: 36th International Symposium on Intensive Care and Emergency Medicine

Critical Care (2016)

Author et al R. M. Bateman Michael D. Sharpe Justin E. Jagger Chiara Ellis

[This corrects the article DOI: 10.1186/s13054-016-1208-6.].

10.1186/s13054-016-1358-6

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Citations (8)

On the pathophysiology and management of cellulitis

Duncan R Cranendonk

Cellulitis is a bacterial skin and soft tissue infection. It is one of the most common infections requiring hospitalization, and one of the most common reasons for prescribing antibiotics. Despite the fact that it is a very visible infection, the underlying etiology is poorly understood. Many patients experience recurrences after the initial infection. Even though we have effective treatment options, studies on the most optimal or effective treatment are scarce. Recent concerns regarding antibiotic resistance have prompted studies to evaluate the minimum effective treatment duration in order to reduce antibiotic consumption. Reducing antibiotic consumption should lower the selective pressure that drives antibiotic resistance development. This thesis contains several studies. The most prominent one is a trial comparing the standard antibiotic therapy duration with a shorter therapy duration in patients hospitalized with cellulitis. Furthermore, current evidence on risk factors and etiology have been bundled into a novel model for the development of cellulitis. The skin microbiota of cellulitis patients has been analyzed in an effort to find correlations between aspects of the skin microbiota and the causative agent or disease characteristics. Changes in the coagulation and fibrinolysis system during cellulitis have been investigated. Finally, it shows the characteristics, clinical management and outcomes of a group of patients with cellulitis on the intensive care units. Thus, this thesis is on the pathophysiology and management of cellulitis.

Etiology

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Host innate immune responses to sepsis

Virulence (2013)

W. Joost Wiersinga Stije J. Leopold Duncan R Cranendonk Tom van der Poll

The immune response to sepsis can be seen as a pattern recognition receptor-mediated dysregulation of the immune system following pathogen invasion in which a careful balance between inflammatory and anti-inflammatory responses is vital. Invasive infection triggers both pro-inflammatory and anti-inflammatory host responses, the magnitude of which depends on multiple factors, including pathogen virulence, site of infection, host genetics, and comorbidities. Toll-like receptors, the inflammasomes, and other pattern recognition receptors initiate the immune response after recognition of danger signals derived from microorganisms, so-called pathogen-associated molecular patterns or derived from the host, so-called danger-associated molecular patterns. Further dissection of the role of host–pathogen interactions, the cytokine response, the coagulation cascade, and their multidirectional interactions in sepsis should lead toward the development of new therapeutic strategies in sepsis.

Pathogen-associated molecular pattern

10.4161/viru.25436

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Citations (404)