Leukocyte migration is a key event both in host defense against invading pathogens as well as in inflammation. Bacteria generate chemoattractants primarily by excretion (formylated peptides), complement activation (C5a), and subsequently through activation of leukocytes (e.g., leukotriene B4, platelet-activating factor, and interleukin 8). Here we describe a new protein secreted by Staphylococcus aureus that specifically impairs the response of neutrophils and monocytes to formylated peptides and C5a. This chemotaxis inhibitory protein of S. aureus (CHIPS) is a 14.1-kD protein encoded on a bacteriophage and is found in >60% of clinical isolates. CHIPS reduces the neutrophil recruitment toward C5a in a mouse peritonitis model, even though its activity is much more potent on human than on mouse cells. These findings suggest a new immune escape mechanism of S. aureus and put forward CHIPS as a potential new antiinflammatory therapeutic compound.

A prospective cohort study was performed among travelers from the Netherlands to investigate the acquisition of carbapenemase-producing Enterobacteriaceae (CP-E) and extended-spectrum β-lactamase–producing Enterobacteriaceae (ESBL-E) and associated risk factors. Questionnaires were administered and rectal swab samples were collected and tested before and after traveler return. Of 370 travelers, 32 (8.6%) were colonized with ESBL-E before trave,; 113 (30.5%) acquired an ESBL-E during travel, and 26 were still colonized 6 months after return. No CP-E were found. Independent risk factors for ESBL-E acquisition were travel to South and East Asia. Multilocus sequence typing showed extensive genetic diversity among Escherichia coli. Predominant ESBLs were CTX-M enzymes. The acquisition rate, 30.5%, of ESBL-E in travelers from the Netherlands to all destinations studied was high. Active surveillance for ESBL-E and CP-E and contact isolation precautions may be recommended at admission to medical facilities for patients who traveled to Asia during the previous 6 months.

The emergence of the plasmid-mediated mcr colistin resistance gene in the community poses a potential threat for treatment of patients, especially when hospitalized. The aim of this study was to determine the prevalence of all currently known mcr mediated colistin resistance gene in fecal samples of patients attending a tertiary care hospital. From November 2014 until July 2015, fecal samples of patients attending the Leiden University Medical Center were collected and screened for presence of mcr using real-time PCR. Two of 576 patients were positive for mcr-1, resulting in a prevalence of 0.35%, whereas no mcr-2 was found. One of these samples was culture negative, the second sample contained a blaCMY-2 and mcr-1 containing E.coli. This strain belonged to Sequence Type 359 and serotype O177:H21. The mcr-1 containing E.coli was phenotypically susceptible to colistin with a MIC of ≤ 0.25mg/l, due to a 1329bp transposon IS10R inserted into the mcr-1 gene as identified by WGS. This prevalence study shows that mcr-1 is present in low levels patients out of the community attending a hospital. Furthermore the study underlines the importance of phenotypical confirmation of molecular detection of a mcr-1 gene.

In a previous study, we showed that Staphylococcus aureus supernate (SaS) is a potent agonist for both neutrophils and mononuclear cells. To further investigate the immunomodulating effects of SaS, the effect on different neutrophil receptors was studied. Expression of various neutrophil receptors, before and after treatment with SaS, was quantified by flow cytometry. We found that SaS treatment of neutrophils resulted in a specific and total downregulation of the C5a and the fMLP receptor, both serpentine receptors, while other receptors were totally unaffected. Since these two receptors are both involved in chemotaxis, we tested the effect of SaS in calcium flux and chemotaxis assays. We showed that preincubation with SaS abrogated the rise in intracellular calcium concentration upon triggering with fMLP and C5a. We also showed that SaS is a potent inhibitor of neutrophil chemotaxis towards fMLP and C5a, but does not interfere with chemotaxis towards interleukin-8. These findings indicate that S. aureus produces a virulence factor extracellularly, which impairs chemotaxis towards the infected site.

In this paper we aim to provide insight into the complexity of outbreak management in an intensive care unit (ICU) setting. In October 2010 four patients on the ICU of our tertiary care centre were colonized or infected with a multidrug-resistant strain of Pseudomonas aeruginosa (MDR-PA). An outbreak investigation was carried out and infection control measures were taken in an attempt to identify a potential source and stop transmission. The outbreak investigation included descriptive epidemiology, comprising retrospective case finding by reviewing the laboratory information system back to 2004 and prospective case finding by patient screening for MDR-PA. Furthermore, microbiological analysis, environmental screening and a case-control study were carried out. Infection control measures consisted of re-education of healthcare personnel on basic hygiene measures, auditing of hygiene procedures used in daily practice by infection control practitioners, and stepwise up-regulation of isolation measures. From February 2009 to January 2012, 44 patients on our ICU were found to be MDR-PA positive. MDR-PA isolates of the 44 patients showed two distinct AFLP patterns, with homology within each of the AFLP clusters of more than 93%. The VIM metallo-β-lactamase gene was detected in 20 of 21 tested isolates. A descriptive epidemiology investigation identified the rooms with the highest numbers of MDR-PA positive patients. The case-control study showed three factors to be independently associated with MDR-PA positivity: admission to ICU subunit 1 (OR, 6.1; 95% CI, 1.7, 22), surgery prior to or during admission (OR, 5.7; 95% CI, 1.6, 20) and being warmed-up with the warm-air blanket (OR, 3.6; 95% CI, 1.2, 11). After three environmental screening rounds, with sampling of sinks, furniture and devices in the ICU, without revealing a clear common source, a fourth environmental investigation included culturing of faucet aerators. Two faucets were found to be positive for MDR-PA and were replaced. The occurrence of new cases decreased with the strengthening of infection control measures and declined further with the removal of the common source. With this integrated approach a prolonged outbreak of P. aeruginosa was controlled. Contaminated faucet aerators on the ICU probably served as a persisting source, while interpatient transmission by medical staff was a likely way of spread. Seven months after the last case (January 2012) and 3 months after cessation of extended isolation measures (May 2012), single cases started to occur on the ICU, with a total of seven patients in the past year. No common source has yet been found.