Prevention of severe infectious complications after colorectal surgery using oral non-absorbable antimicrobial prophylaxis: results of a multicenter randomized placebo-controlled clinical trial.

BACKGROUND: Surgical site infections (SSIs) are common complications after colorectal surgery. Oral non-absorbable antibiotic prophylaxis (OAP) can be administered preoperatively to reduce the risk of SSIs. Its efficacy without simultaneous mechanical cleaning is unknown. METHODS: The Precaution trial was a double-blind, placebo-controlled randomized clinical trial conducted in six Dutch hospitals. Adult patients who underwent elective colorectal surgery were randomized to receive either a three-day course of preoperative OAP with tobramycin and colistin or placebo. The primary composite endpoint was the incidence of deep SSI or mortality within 30 days after surgery. Secondary endpoints included both infectious and non-infectious complications at 30 days and six months after surgery. RESULTS: The study was prematurely ended due to the loss of clinical equipoise. At that time, 39 patients had been randomized to active OAP and 39 to placebo, which reflected 8.1% of the initially pursued sample size. Nine (11.5%) patients developed the primary outcome, of whom four had been randomized to OAP (4/39; 10.3%) and five to placebo (5/39; 12.8%). This corresponds to a risk ratio in the intention-to-treat analysis of 0.80 (95% confidence interval (CI) 0.23-2.78). In the per-protocol analysis, the relative risk was 0.64 (95% CI 0.12-3.46). CONCLUSIONS: Observational data emerging during the study provided new evidence for the effectiveness of OAP that changed both the clinical and medical ethical landscape for infection prevention in colorectal surgery. We therefore consider it unethical to continue randomizing patients to placebo. We recommend the implementation of OAP in clinical practice and continuing monitoring of infection rates and antibiotic susceptibilities. TRIAL REGISTRATION: The PreCaution trial is registered in the Netherlands Trial Register under NL5932 (previously: NTR6113) as well as in the EudraCT register under 2015-005736-17.

REtrieval And cure of Chronic Hepatitis C (REACH): Results of micro-elimination in the Utrecht province.

BACKGROUND: The Netherlands is one of the six European countries considered on track to eliminate hepatitis C virus by 2030. To achieve this goal, continuous efforts have to be put into designing efficient case-finding strategies, including the retrieval of previously diagnosed hepatitis C virus-infected who are lost to follow-up. AIMS: To trace and treat all lost to follow-up hepatitis C virus patients in the Utrecht region and create an efficient retrieval strategy that can be used in future (national) retrieval initiatives. METHODS: Positive hepatitis C virus diagnostic tests (anti-hepatitis C virus IgG or hepatitis C virus-RNA) from the laboratory of all four hospitals and one central laboratory for primary care diagnostics in the province of Utrecht from 2001 to 2015 were linked to clinical records. Untreated patients with available contact information were deemed eligible for retrieval and invited for reevaluation with (virology) blood tests, fibroscan measurement and possible direct-acting antiviral therapy. MAIN RESULTS: After screening all hepatitis C virus diagnostics, 1913 chronic hepatitis C virus-infected were identified of which 14.1% (n = 269) were invited back into care. Overall, 17.4% was traced with the highest yield (28.3%) in those who lived in the Utrecht province. Through renewed patient assessments, 42 chronic hepatitis C virus infections were re-identified (76% with a history of intravenous drug use, 24% with Metavir F3-F4). Until now, 59% has either scheduled or initiated direct-acting antiviral therapy. CONCLUSION: The retrieval of previously diagnosed hepatitis C virus patients through screening of laboratory diagnostics from the past is feasible and should be pursued for further control and reduction of hepatitis C virus infection. Retrieval is most successful when performed regionally. LAY SUMMARY: To completely eliminate chronic hepatitis C virus (HCV) infection and prevent complications, undiagnosed and also previously diagnosed but lost to follow-up (LFU) HCV patients have to be brought (back) into care for therapy. Retrieval of LFU HCV patients through screening of laboratory diagnostics from the past is feasible and most successful when performed regionally.

Staphylococcus aureus formyl peptide receptor-like 1 inhibitor (FLIPr) and its homologue FLIPr-like are potent FcγR antagonists that inhibit IgG-mediated effector functions.

To evade opsonophagocytosis, Staphylococcus aureus secretes various immunomodulatory molecules that interfere with effective opsonization by complement and/or IgG. Immune-evasion molecules targeting the phagocyte receptors for these opsonins have not been described. In this study, we demonstrate that S. aureus escapes from FcγR-mediated immunity by secreting a potent FcγR antagonist, FLIPr, or its homolog FLIPr-like. Both proteins were previously reported to function as formyl peptide receptor inhibitors. Binding of FLIPr was mainly restricted to FcγRII receptors, whereas FLIPr-like bound to different FcγR subclasses, and both competitively blocked IgG-ligand binding. They fully inhibited FcγR-mediated effector functions, including opsonophagocytosis and subsequent intracellular killing of S. aureus by neutrophils and Ab-dependent cellular cytotoxicity of tumor cells by both neutrophils and NK cells. In vivo, treatment of mice with FLIPr-like prevented the development of an immune complex-mediated FcγR-dependent Arthus reaction. This study reveals a novel immune-escape function for S. aureus-secreted proteins that may lead to the development of new therapeutic agents in FcγR-mediated diseases.

Role of healthcare workers in outbreaks of methicillin-resistant Staphylococcus aureus: a 10-year evaluation from a Dutch university hospital.

BACKGROUND AND OBJECTIVE: The benefit of screening healthcare workers (HCWs) at risk for methicillin-resistant Staphylococcus aureus (MRSA) carriage and furloughing MRSA-positive HCWs to prevent spread to patients is controversial. We evaluated our MRSA program for HCWs between 1992 and 2002. SETTING: A university medical center in The Netherlands, where methicillin resistance has been kept below 0.5% of all nosocomial S. aureus infections using active surveillance cultures and isolation of colonized patients. DESIGN: HCWs caring for MRSA-positive patients or patients in foreign hospitals were screened for MRSA. MRSA-positive HCWs had additional cultures, temporary exclusion from patient-related work, assessment of risk factors for persisting carriage, decolonization therapy with mupirocin intranasally and chlorhexidine baths for skin and hair, and follow-up cultures. RESULTS: Fifty-nine HCWs were colonized with MRSA. Seven of 840 screened employees contracted MRSA in foreign hospitals; 36 acquired MRSA after contact with MRSA-positive patients despite isolation precautions (attack rate per outbreak varied from less than 1% to 15%). Our hospital experienced 17 MRSA outbreaks, including 13 episodes in which HCWs were involved. HCWs were index cases of at least 4 outbreaks. In 8 outbreaks, HCWs acquired MRSA after caring for MRSA-positive patients despite isolation precautions. CONCLUSION: Postexposure screening of HCWs allowed early detection of MRSA carriage and prevention of subsequent transmission to patients. Where the MRSA prevalence is higher, the role of HCWs may be greater. In such settings, an adapted version of our program could help prevent dissemination.

Surveillance for hospital-acquired infections on surgical wards in a Dutch university hospital.

OBJECTIVES: To determine incidence rates of hospital-acquired infections and to develop preventive measures to reduce the risk of hospital-acquired infections. METHODS: Prospective surveillance for hospital-acquired infections was performed during a 5-year period in the wards housing general and vascular, thoracic, orthopedic, and general gynecologic and gynecologic-oncologic surgery of the University Medical Center Utrecht, the Netherlands. Data were collected from patients with and without infections, using criteria of the Centers for Disease Control and Prevention. RESULTS: The infection control team recorded 648 hospital-acquired infections affecting 550 (14%) of 3,845 patients. The incidence density was 17.8 per 1,000 patient-days. Patients with hospital-acquired infections were hospitalized for 19.8 days versus 7.7 days for patients without hospital-acquired infections. Prolongation of stay among patients with hospital-acquired infections may have resulted in 664 fewer admissions due to unavailable beds. Different specialties were associated with different infection rates at different sites, requiring a tailor-made approach. Interventions were recommended for respiratory tract infections in the thoracic surgery ward and for surgical-site infections in the orthopedic and gynecologic surgery wards. CONCLUSIONS: Surveillance in four surgical wards showed that each had its own prominent infection, risk factors, and indications for specific recommendations. Because prospective surveillance requires extensive resources, we considered a modified approach based on a half-yearly point-prevalence survey of hospital-acquired infections in all wards of our hospital. Such surveillance can be extended with procedure-specific prospective surveillance when indicated.

Influence of cytomegalovirus seropositivity on outcome after T cell-depleted bone marrow transplantation: contrasting results between recipients of grafts from related and unrelated donors.

We analyzed the effect of cytomegalovirus (CMV) serostatus on overall survival (OS) and transplant-related mortality (TRM) in 253 consecutively treated patients receiving partially T cell-depleted (TCD) bone marrow from either matched related donors (MRDs; n=205) or matched unrelated donors (MUDs; n=48). Short-course, low-dose preemptive therapy with ganciclovir was provided as soon as a positive antigenemia assay result was obtained. Ganciclovir prophylaxis, which was identical to preemptive therapy, was given to patients with acute graft-versus-host disease (GVHD) grades II-IV who had to be treated with high-dose steroids. In recipients of transplants from MRDs, inferior OS and increased TRM were predicted by extensive chronic GVHD (P<.001). High-risk disease status and older age adversely influenced OS (P=.001) and TRM (P=.002), respectively; older age resulted in a trend toward decreased OS (P=.066). In recipients of transplants from MUDs, OS and TRM were strongly influenced by patient CMV seropositivity (P=.013 and.007, respectively). In conclusion, CMV seropositivity is not an adverse risk factor for OS and TRM in recipients of transplants from MRDs. However, in recipients of transplants from MUDs, patient CMV seropositivity strongly affects OS and TRM.