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.

The burden of bacteremic and non-bacteremic Gram-negative infections: A prospective multicenter cohort study in a low-resistance country.

Objectives There is a global increase in infections caused by Gram-negative bacteria. The majority of research is on bacteremic Gram-negative infections (GNI), leaving a knowledge gap on the burden of non-bacteremic GNI. Our aim is to describe characteristics and determine the burden of bacteremic and non-bacteremic GNI in hospitalized patients in the Netherlands. Methods We conducted a prospective cohort study of patients in eight hospitals with microbiologically confirmed GNI, between June 2013 and November 2015. In each hospital the first five adults meeting the eligibility criteria per week were enrolled. We estimated the national incidence and mortality of GNI by combining the cohort data with a national surveillance database for antimicrobial resistance. Results 1,954 patients with GNI were included of which 758 (39%) were bloodstream infections (BSI). 243 GNI (12%) involved multi-drug resistant pathogens. 30-day mortality rate was 11.1% (n = 217) Estimated national incidences of non-bacteremic GNI and bacteremic GNI in hospitalized adults were 74 (95% CI 58 - 89) and 86 (95% CI 72-100) per 100,000 person years, yielding estimated annual numbers of 30-day all-cause mortality deaths of 1,528 (95% CI 1,102-1,954) for bacteremic and 982 (95% CI 688 - 1,276) for non-bacteremic GNI. Conclusion GNI form a large mortality burden in a low-resistance country. A third of the associated mortality occurs after non-bacteremic GNI.

Attributable mortality of antibiotic resistance in gram-negative infections in the Netherlands: a parallel matched cohort study.

OBJECTIVES: Antibiotic resistance in Gram-negative bacteria has been associated with increased mortality. This was demonstrated mostly for third-generation cephalosporin-resistant (3GC-R) Enterobacterales bacteraemia in international studies. Yet, the burden of resistance specifically in the Netherlands and created by all types of Gram-negative infection has not been quantified. We therefore investigated the attributable mortality of antibiotic resistance in Gram-negative infections in the Netherlands. METHODS: In eight hospitals, a sample of Gram-negative infections was identified between 2013 and 2016, and separated into resistant and susceptible infection cohorts. Both cohorts were matched 1:1 to non-infected control patients on hospital, length of stay at infection onset, and age. In this parallel matched cohort set-up, 30-day mortality was compared between infected and non-infected patients. The impact of resistance was then assessed by dividing the two separate risk ratios (RRs) for mortality attributable to Gram-negative infection. RESULTS: We identified 1954 Gram-negative infections, of which 1190 (61%) involved Escherichia coli, 210 (11%) Pseudomonas aeruginosa, and 758 (39%) bacteraemia. Resistant Gram-negatives caused 243 infections (12%; 189 (78%) 3GC-R Enterobacterales, nine (4%) multidrug-resistant P. aeruginosa, no carbapenemase-producing Enterobacterales). Subsequently, we matched 1941 non-infected controls. After adjustment, point estimates for RRs comparing mortality between infections and controls were similarly higher than 1 in case of resistant infections and susceptible infections (1.42 (95% confidence interval 0.66-3.09) and 1.32 (1.06-1.65), respectively). By dividing these, the RR reflecting attributable mortality of resistance was calculated as 1.08 (0.48-2.41). CONCLUSIONS: In the Netherlands, antibiotic resistance did not increase 30-day mortality in Gram-negative infections.

The First Two Cases of Candida auris in The Netherlands.

Candida auris is a rapidly emerging multidrug-resistant pathogenic yeast. In recent years, an increasing number of C. auris invasive infections and colonized patients have been reported, and C. auris has been associated with hospital outbreaks worldwide, mainly in intensive care units (ICUs). Here, we describe the first two cases of C. auris in The Netherlands. Both cases were treated in a healthcare facility in India prior to admission. The patients were routinely placed in contact precautions in a single room after admission, which is common practice in The Netherlands for patients with hospitalization outside The Netherlands. No transmission of C. auris was noticed in both hospitals. Routine admission screening both for multidrug-resistant (MDR) bacteria and MDR yeasts should be considered for patients admitted from foreign hospitals or countries with reported C. auris transmission.

Usefulness of aqueous humor analysis for the diagnosis of posterior uveitis.

PURPOSE: To assess the clinical usefulness of aqueous fluid analysis for the diagnosis and treatment of patients suspected of having infectious posterior uveitis (PU). DESIGN: Case-control study. PARTICIPANTS: From 2002 through 2005, 152 eyes from 152 patients with active PU (16 of whom were immunosuppressed) underwent diagnostic aqueous testing. As controls, 20 patients with Fuchs' heterochromic uveitis and 20 patients with age-related cataract were included. METHODS: Aqueous samples were examined by real-time polymerase chain reaction (PCR) and by pathogen-specific analysis of intraocular antibody production (Goldmann-Witmer coefficient [GWC]) for herpes simplex virus (HSV), varicella zoster virus (VZV), cytomegalovirus (CMV), and the parasite Toxoplasma gondii. MAIN OUTCOME MEASURES: Results of aqueous analysis and any adverse effects of aqueous sampling. Correlations between the results of aqueous testing and clinical characteristics as well as the treatment of patients. RESULTS: Of 152 patients, 44 (29%) had positive results for at least one diagnostic assay (37/136 [28%] immunocompetent and 7/16 [44%] immunocompromised patients). None of the controls had positive results using PCR or GWC. A positive result was obtained predominantly in patients with focal chorioretinitis (37/87 [40%]) and in extensive retinitis (7/9 [78%]), whereas in multifocal chorioretinitis, neuroretinitis, and retinal vasculitis only a few samples demonstrated positive results (2/19, 1/29, and 0/10, respectively). Of 37 immunocompetent PU patients with positive results, 28 (76%) cases were caused by T. gondii, whereas viral infections were most common in immunocompromised patients (5/7 [71%]). In immunocompetent and toxoplasmosis PU patients, GWC was the most informative assay (34/37 [92%] and 28/30 [93%], respectively), in contrast to immunosuppressed patients (PCR positive in 5/7 and GWC positive in 4/7). Independent of the immune status of patients, positive PCR results were observed more frequently in viral infections than in toxoplasmosis (P<0.001). As a consequence of aqueous analysis, change of treatment was necessary in 36 patients (24%). None of the patients experienced complications during or after aqueous sampling. CONCLUSIONS: Despite the posterior location of inflammation, aqueous analyses with PCR and GWC for HSV, VZV, CMV, and T. gondii revealed an infectious cause in 29% of patients with PU.

Rubella virus is associated with fuchs heterochromic iridocyclitis.

PURPOSE: To determine whether rubella virus (RV) is involved in the pathogenesis of Fuchs heterochromic iridocyclitis (FHI). DESIGN: Retrospective patient-controlled study. METHODS: Intraocular immunoglobulin G production against RV, herpes simplex virus (HSV), varicella zoster virus (VZV), and Toxoplasma gondii was determined in the aqueous humor of 14 patients with FHI, 13 control subjects with herpetic uveitis anterior, and 19 control subjects with ocular toxoplasmosis by calculation of the Goldmann-Witmer coefficient (GWC). RESULTS: All patients and control subjects were seropositive for RV. Intraocular antibody production (GWC >3) against RV was found in 13 of 14 patients (93%) with FHI. Intraocular antibody production against HSV, VZV, or T gondii was not detected. None of the control subjects with herpetic uveitis anterior or with toxoplasma chorioretinitis had a positive GWC for rubella virus (P < .0001, Fisher exact test). CONCLUSION: Rubella virus, but not HSV, VZV, or T gondii, is associated with FHI.

Polymerase chain reaction and Goldmann-Witmer coefficient analysis are complimentary for the diagnosis of infectious uveitis.

PURPOSE: To determine the relative contribution of the analysis of intraocular antibody production and the polymerase chain reaction (PCR) in aqueous humor (AH) to the diagnosis of infectious uveitis. DESIGN: Retrospective case-control study. METHODS: Paired AH and serum samples from 230 patients suspected of infectious uveitis were examined for intraocular antibody production against herpes simplex virus (HSV), varicella zoster virus (VZV), and Toxoplasma gondii by calculating the Goldmann-Witmer coefficient (GWC). In addition, AH samples were investigated by real-time PCR to determine the presence of microbial DNA. RESULTS: Positive results were obtained in 54 cases (23%): 13 HSV (24%), 16 VZV (30%), and 25 T gondii (46%). Of these, 23 (43%) were positive for both GWC and PCR, 26 (48%) only for GWC, and 5 (9%) only for PCR. With PCR as the sole diagnostic approach, a correct diagnosis of the infectious etiology would have been missed in 34% of cases for the herpes viruses and in 64% for T gondii. Analysis of the relationship between a positive laboratory diagnosis and the time of sampling after onset of ocular disease demonstrated that intraocular antibody production was found throughout the course of the diseases. Viral DNA was more readily detected early in infection. In contrast, T gondii nucleic acid was not detected until 3 weeks after onset of ocular disease. CONCLUSIONS: Analysis of intraocular antibody production contributed considerably to the etiological diagnosis of infectious uveitis, most notably of ocular toxoplasmosis early after onset of disease. Therefore, both PCR and GWC determination might be performed for comprehensive diagnosis of intraocular infections.

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.

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.