Complicated Carriage with Methicillin-Resistant Staphylococcus aureus: Evaluation of the Effectiveness of Decolonization Regimens Advised in the Dutch National Guideline.

Methicillin-resistant Staphylococcus aureus (MRSA) colonization leads to increased infection rates and mortality. Decolonization treatment has been proven to prevent infection and reduce transmission. As the optimal antimicrobial strategy is yet to be established, different regimens are currently prescribed to patients. This study aimed to evaluate the efficacy of the decolonization treatments recommended by the Dutch guideline. A retrospective multicenter cohort study was conducted in five Dutch hospitals. All patients who visited the outpatient clinic because of complicated MRSA carriage between 2014 and 2018 were included. We obtained data on patient characteristics, clinical and microbiological variables relevant for MRSA decolonization, environmental factors, decolonization regimen, and treatment outcome. The primary outcome was defined as three negative MRSA cultures after treatment completion. Outcomes were stratified for the first-line treatment strategies. A total of 131/224 patients were treated with systemic antibiotic agents. Treatment was successful in 111/131 (85%) patients. The success rate was highest in patients treated with doxycycline-rifampin (32/37; 86%), but the difference from any of the other regimens did not reach statistical significance. There was no difference in the success rate of a 7-day treatment compared to that with 10 to 14 days of treatment (odds ratio [OR], 0.99; 95% confidence interval [CI], 0.39 to 2.53; P = 1.00). Side effects were reported in 27/131 (21%) patients and consisted mainly of mild gastrointestinal complaints. In a multivariable analysis, an immunocompromised status was an independent risk factor for failure at the first treatment attempt (OR, 4.65; 95% CI, 1.25 to 17.25; P = 0.02). The antimicrobial combinations recommended to treat complicated MRSA carriage yielded high success rates. Prolonged treatment did not affect treatment outcome. A randomized trial is needed to resolve whether the most successful regimen in this study (doxycycline plus rifampin) is superior to other combinations.

Ex vivo lymphocyte phenotyping during Plasmodium falciparum sporozoite immunization in humans.

Immunization of malaria-naïve volunteers under chemoprophylaxis with Plasmodium falciparum sporozoites (CPS) efficiently and reproducibly induces sterile protection and thus constitutes an excellent model to study protective immune responses against malaria. Here, we performed the first longitudinal assessment of lymphocyte activation and differentiation kinetics during sporozoite immunization in 15 volunteers by ex vivo lymphocyte flow cytometry analysis. Both CD4 and CD8 T cells as well as γδT cells, NK cells and CD3+ CD56+ cells showed increased activation and proliferation following immunization. Transient induction of the transcription factor T-bet and the cytotoxic molecule granzyme B indicated a role of Th1 responses and cytotoxic T cells in CPS-induced immunity. The absolute number of γδT cells as well as the proportion of granzyme B-containing γδT cells showed a significant and sustained increase. Regulatory T-cell (Treg) proliferation was significantly higher after the second immunization in subjects subsequently not protected against challenge infection. These findings indicate an important role for γδT cells, Th1 and cytotoxic responses in whole sporozoite immunization with a possibly suppressive role of Tregs.

Intradermal vaccination to protect against yellow fever and influenza.

The viral infections yellow fever and influenza can lead to large epidemics, which may deplete limited vaccine supplies. The intradermal vaccination route of yellow fever and influenza vaccines has received renewed attention, because it allows dose reduction without loss of efficacy. In this chapter, we review these two vaccines, the history of vaccine development, correlates of protection, immune response to vaccination and current knowledge concerning intradermal vaccination, including the immunological background, both in healthy subjects and immunocompromized individuals.

Erratum to "Measles outbreaks - potential threat for health care professionals" Infect Prev Pract, Volume 2, Issue 3, September 2020, 100074.

[This corrects the article DOI: 10.1016/j.infpip.2020.100074.].

Outcome of Debridement, Antibiotics, and Implant Retention for Staphylococcal Hip and Knee Prosthetic Joint Infections, Focused on Rifampicin Use: A Systematic Review and Meta-Analysis.

The treatment of staphylococcal prosthetic joint infection (PJI) with debridement, antibiotics, and retention of the implant (DAIR) often results in failure. An important evidence gap concerns the treatment with rifampicin for PJI. A systematic review and meta-analysis were conducted to assess the outcome of staphylococcal hip and/or knee PJI after DAIR, focused on the role of rifampicin. Studies published until September 2, 2020 were included. Success rates were stratified for type of joint and type of micro-organism. Sixty-four studies were included. The pooled risk ratio for rifampicin effectiveness was 1.10 (95% confidence interval, 1.00-1.22). The pooled success rate was 69% for Staphylococcus aureus hip PJI, 54% for S aureus knee PJI, 83% for coagulase-negative staphylococci (CNS) hip PJI, and 73% for CNS knee PJI. Success rates for MRSA PJI (58%) were similar to MSSA PJI (60%). The meta-analysis indicates that rifampicin may only prevent a small fraction of all treatment failures.

Short-term outpatient follow-up of COVID-19 patients: A multidisciplinary approach.

BACKGROUND: Short-term follow-up of COVID-19 patients reveals pulmonary dysfunction, myocardial damage and severe psychological distress. Little is known of the burden of these sequelae, and there are no clear recommendations for follow-up of COVID-19 patients.In this multi-disciplinary evaluation, cardiopulmonary function and psychological impairment after hospitalization for COVID-19 are mapped. METHODS: We evaluated patients at our outpatient clinic 6 weeks after discharge. Cardiopulmonary function was measured by echocardiography, 24-hours ECG monitoring and pulmonary function testing. Psychological adjustment was measured using questionnaires and semi-structured clinical interviews. A comparison was made between patients admitted to the general ward and Intensive care unit (ICU), and between patients with a high versus low functional status. FINDINGS: Eighty-one patients were included of whom 34 (41%) had been admitted to the ICU. New York Heart Association class II-III was present in 62% of the patients. Left ventricular function was normal in 78% of patients. ICU patients had a lower diffusion capacity (mean difference 12,5% P = 0.01), lower forced expiratory volume in one second and forced vital capacity (mean difference 14.9%; P<0.001; 15.4%; P<0.001; respectively). Risk of depression, anxiety and PTSD were 17%, 5% and 10% respectively and similar for both ICU and non-ICU patients. INTERPRETATION: Overall, most patients suffered from functional limitations. Dyspnea on exertion was most frequently reported, possibly related to decreased DLCOc. This could be caused by pulmonary fibrosis, which should be investigated in long-term follow-up. In addition, mechanical ventilation, deconditioning, or pulmonary embolism may play an important role.

Healthcare-seeking strategies among displaced children in war-ridden northern Uganda: the case of malaria.

A field study was performed to examine suffering and treatment seeking from the perspective of children aged 8-16 years living in war-affected northern Uganda. Various techniques for collecting qualitative and quantitative data were used, including a semi-structured questionnaire about illness experiences and medicine use over a 1-month recall period. The 165 children who were interviewed were attending primary schools for displaced children and/or commuters' night shelters. The children frequently attributed their common febrile ailments to malaria and used a variety of pharmaceuticals and herbal remedies, as self-medication, for their self-diagnosed malarial episodes. Misdiagnosis of febrile illnesses by the children (as well as by the local healthcare providers) and frequent misuse of medicines in the treatment of these illnesses appeared to be very common. Improvement of the health conditions of these children requires a change of focus. Firstly, children above the age of 5 years who are not under adult care and who are often no longer welcome in the local hospital's paediatric ward need to be accepted at the outpatient clinics currently intended for adults. Secondly, the local diagnostic system needs to be improved, not only so that malaria can be reliably diagnosed but also so that alternative diagnoses can be confirmed or rejected, otherwise the current over-consumption of antimalarial drugs may simply be replaced with an over-consumption of antibiotics.

Limited multi-drug resistant organism related stigma in carriers exposed to isolation precautions: an exploratory quantitative questionnaire study.

BACKGROUND: Isolation precautions are applied to control the risk of transmission of multi-drug resistant organisms (MDROs). These precautions have been associated with adverse effects, such as anxiety and depression. This study aimed to quantify stigma among MDRO carriers and its association with perceived mental health and experienced quality of care. METHODS: A quantitative questionnaire study was performed in MDRO carriers exposed to ≥3 days of isolation precautions during hospitalization. Items derived from the Consumer Quality Index questionnaire (CQI) were used to assess perception of care. Stigma scores were calculated using the recently modified Berger Stigma Scale for meticillin-resistant Staphylococcus aureus (MRSA). Mental health was measured with the RAND Mental Health Inventory. The Spearman rank correlation test was used to assess the association between stigma score and RAND mental health score. FINDINGS: Of the 41 included carriers, 31 (75.6%) completed both questionnaires. The experienced quality of care was 'good' according to CQI score. Twenty-four percent reported not to have received proper explanation about MDRO carriership from healthcare workers (HCWs). MDRO-associated stigma was reported in 1/31 (3.2%). Poor mental health was self-reported in 3/31 (9.7%). There was no correlation between stigma score and RAND mental health score (Spearman correlation coefficient: 0.347). CONCLUSIONS: In this study, MDRO carriers exposed to ≥3 days of isolation precautions did not report stigma. This contrasts with a recent study that investigated MRSA-associated stigma and may be explained by contact plus airborne isolation protocols in MRSA compared with contact isolation alone in most other MDROs. Also, the psychological impact may be of a different magnitude due to as yet unknown reasons.

Measles outbreaks - potential threat for health care professionals.

The ongoing spread of measles is a major concern for public health. Optimal vaccination coverage amongst health care professionals (HCP) is essential for individual protection. This is illustrated by our two cases of measles infection in HCP during the 2018 outbreak in Europe. We developed a questionnaire to assess protection against measles amongst HCP working in acute care of a tertiary hospital in The Netherlands. In total, 29% of these professionals were not protected against measles. During current worldwide measles outbreaks, it is paramount for employee health protection, patient protection and disease control to register and optimize employees' immunity.

Long-term immunogenicity after yellow fever vaccination in immunosuppressed and healthy individuals.

BACKGROUND: The live-attenuated yellow fever vaccine (YFV) is generally contraindicated in immunosuppressed patients. Our aim was to investigate if immunosuppressive therapy impairs the long-term protection against yellow fever virus in patients who had received YFV prior to the start of their immunosuppressive therapy. METHODS: Our study examined 35 healthy individuals and 40 immunosuppressed patients with autoimmune diseases or organ transplants. All individuals had received YFV prior to the onset of their immunosuppression. We analysed the long-term influence of the immunosuppressive therapy on the YFV protective immunity by measuring neutralising antibodies (NA) with the Plaque Reduction Neutralisation Test (PRNT). We assessed risk factors for a negative PRNT result (titre below 1: 10) and their influence on the magnitude of the NA. RESULTS: A median time interval of 21.1 years (interquartile range 14.4-31.3 years) after the YFV in all patients, a total of 35 immunosuppressed patients (88%) were seropositive (PRNT ≥ 1:10) compared to 31 patients (89%) in the control group. The geometric mean titres of NA did not differ between the groups. The duration of an underlying rheumatic disease was the only risk factor found for a lower magnitude of NA. An insufficient level of NA was found in nine subjects (12%) who had received a single dose of YFV (in one subject, the number of YFV doses was unknown). CONCLUSION: The use of an immunosuppressive drug started after the administration of the YFV did not affect long-term persistence of NA. A second dose of YFV may be necessary to secure long-term immunity.

Pancytopenia in a simultaneous pancreas and kidney transplant recipient: an unexpected cause - a case of visceral leishmaniasis in a transplant recipient.

A transplant recipient presented with fever and pancytopenia. Bone marrow biopsy showed Leishmania parasites. Travel history revealed a trip to Greece 17 months prior to admission. This case illustrates the importance of considering leishmaniasis as a cause of pancytopenia, especially in the immunocompromised, even in the absence of recent travel to an endemic area. Acknowledgment of this infection is vital as the outcome can be fatal if left untreated.

S. typhi Vi capsular polysaccharide vaccine-induced humoral immunity in travellers with immunosuppressive therapy for rheumatoid disease.

INTRODUCTION: Typhoid fever is a global health problem, causing significant morbidity and mortality. Currently, the most widely used vaccine is the typhoid Vi capsular polysaccharide (Vi-PS) vaccine. While epidemiological studies on its efficacy have been performed in children in endemic countries, there are no efficacy studies evaluating its use in travel medicine. Response to vaccination may differ in travellers receiving immunosuppressive therapy. This study investigates the humoral response to Vi-PS vaccination in travellers receiving immunosuppressive therapy for rheumatoid disease. METHODS: We recruited patients from the LUMC rheumatology outpatient clinic and travellers from the travel clinic who had previously received Vi-PS vaccination and also immunosuppressive therapy for rheumatoid disease. We analysed blood samples acquired from 42 patients over a period of 3 years. We estimated the length of persistence of protective titres using the survival analysis using multiple cut-off values for protection and measured titre half-life and the influence of immunosuppressive medication on titre half-life using mixed models. RESULTS: Anti-Vi-PS antibody levels stayed above 10 EU/ml for a mean of 13.3 years, above 15 EU/ml for a mean of 10.1 years and above 20 EU/ml for a mean of 8.6 years after Vi-PS vaccination. Titre half-life was 7.5 years (95% CI 5.0-14.7 years, P < 0.001). No significant influence of medication on titre half-life was found. CONCLUSION: Both persistence of protective antibody titres and titre half-life are longer than expected based on other studies. This warrants further study in adult volunteers, both in healthy individuals and patients suffering from rheumatoid disease.

Managing invasive aspergillosis in haematological patients in the era of resistance polymerase chain reaction and increasing triazole resistance: A modelling study of different strategies.

OBJECTIVES: Triazole resistance in Aspergillus spp. is emerging and complicates prophylaxis and treatment of invasive aspergillosis (IA) worldwide. New polymerase chain reaction (PCR) tests on broncho-alveolar lavage (BAL) fluid allow for detection of triazole resistance at a genetic level, which has opened up new possibilities for targeted therapy. In the absence of clinical trials, a modelling study delivers estimates of the added value of resistance detection with PCR, and which empiric therapy would be optimal when local resistance rates are known. DESIGN: A decision-analytic modelling study was performed based on epidemiological data of IA, extended with estimated dynamics of resistance rates and treatment effectiveness. Six clinical strategies were compared that differ in use of PCR diagnostics (used vs not used) and in empiric therapeutic choice in case of unknown triazole susceptibility: voriconazole, liposomal amphotericin B (LAmB) or both. Outcome measures were proportion of correct treatment, survival and serious adverse events. RESULTS: Implementing aspergillus PCR tests was projected to result in residual treatment-susceptibility mismatches of <5% for a triazole resistance rate up to 20% (using voriconazole). Empiric LAmB outperformed voriconazole at resistance rates >5-20%, depending on PCR use and estimated survival benefits of voriconazole over LAmB. Combination therapy of voriconazole and LAmB performed best at all resistance rates, but the advantage over the other strategies should be weighed against the expected increased number of drug-related serious adverse events. The advantage of combination therapy over LAmB monotherapy became smaller at higher triazole resistance rates. CONCLUSIONS: Introduction of current aspergillus PCR tests on BAL fluid is an effective way to increase the proportion of patients that receive targeted therapy for IA. The results indicate that close monitoring of background resistance rates and adverse drug events are important to attain the potential benefits of LAmB. The choice of strategy ultimately depends on the probability of triazole resistance, the availability of PCR and individual patient characteristics.

A mobile app for postoperative wound care after arthroplasty: Ease of use and perceived usefulness.

BACKGROUND: Early postoperative discharge after joint arthroplasty may lead to decreased wound monitoring. A mobile woundcare app with an integrated algorithm to detect complications may lead to improved monitoring and earlier treatment of complications. In this study, the ease of use and perceived usefulness of such a mobile app was investigated. OBJECTIVE: Primary objective was to investigate the ease of use and perceived usefulness of using a woundcare app. Secondary objectives were the number of alerts created, the amount of days the app was actually used and patient-reported wound infection. METHODS: Patients that received a joint arthroplasty were enrolled in a prospective cohort study. During 30 postoperative days, patients scored their surgical wound by daily answering of questions in the app. An inbuilt algorithm advised patients to contact their treating physician if needed. On day 15 and day 30, additional questionnaires in the app investigated ease of use and perceived usefulness. RESULTS: Sixty-nine patients were included. Median age was 68 years. Forty-one patients (59.4%) used the app until day 30. Mean grade for ease of use (on a Likert-scale of 1-5) were 4.2 on day 15 and 4.2 on day 30; grades for perceived usefulness were 4.1 on day 15 and 4.0 on day 30. Out of 1317 days of app use, an alert was sent to patients on 29 days (2.2%). Concordance between patient-reported outcome and physician-reported outcome was 80%. CONCLUSIONS: Introduction of a woundcare app with an alert communication on possible wound problems resulted in a high perceived usefulness and ease of use. Future studies will focus on validation of the algorithm and the association between postoperative wound leakage and the incidence of prosthetic joint infection.

Determinants of in-hospital antibiotic prescription behaviour: a systematic review and formation of a comprehensive framework.

BACKGROUND: Knowledge of determinants that influence antibiotic prescription behaviour (APB) is essential for the successful implementation of antimicrobial stewardship interventions. The theory of planned behaviour (TPB) is an established model that describes how cognitions drive human behaviour. OBJECTIVES: The objective of this study was to identify the sociocultural and behavioural determinants that affect APB and to construct a TPB framework of behavioural intent. METHODS: The following online databases were searched: PubMed, Medline, Embase, Web of Science, Cochrane Library and Central. Studies published between July 2010 and July 2017 in European countries, the United States, Canada, New Zealand or Australia were included if they identified one or more determinants of physicians' APB. A systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Based on the TPB, determinants were categorized in behavioural, normative and control beliefs, thus shaping a conceptual framework for APB. RESULTS: Nine studies were eligible for inclusion, and 16 determinants were identified. Determinants relating to fear of adverse outcome (5/9), tolerance of risk and uncertainty (5/9), hierarchy (6/9), and determinants concerning normative beliefs-particularly social team dynamics (6/9)-were most frequently reported. Beliefs about antimicrobial resistance and potential negative consequences of antibiotic use were rarely mentioned. CONCLUSIONS: Behavioural, normative and control beliefs are all relevant in APB. There is a need for quantitative studies to assess the weight of the individual determinants to be able to efficiently design and implement future stewardship interventions. The constructed framework enables a comprehensive approach towards understanding and altering APB.

The effect of anti-tumour necrosis factor alpha treatment on the antibody response to influenza vaccination.

OBJECTIVES: The effect of anti-tumour necrosis factor (TNF) therapy on the antibody responses to vaccines is the subject of ongoing debate. Therefore, we investigated the effect of the three currently available anti-TNF agents on influenza vaccination outcomes in a patient population with long-standing disease. METHODS: In a prospective cohort study, we assessed the antibody response upon influenza vaccination in 112 patients with long-standing autoimmune disease treated with immunosuppressive medication either with anti-TNF (etanercept, adalimumab or infliximab; n = 64) or without anti-TNF (n = 48) and a control group of 18 healthy individuals. Antibody responses were determined by haemagglutination inhibition assay, before and 4 weeks after vaccination. RESULTS: The proportion of individuals with a protective titre (>or=40) after vaccination was large (80-94%) and did not significantly differ between the three groups. Post-vaccination geometric mean antibody titres against influenza (A/H3N2 and B) were significantly lower in the 64 patients treated with anti-TNF compared with the 48 patients not receiving anti-TNF, and the healthy controls. CONCLUSIONS: The antibody response to influenza vaccination in patients treated with anti-TNF is only modestly impaired. The proportion of patients that achieves a protective titre is not significantly diminished by the use of TNF blocking therapies.

[Practical advice for travellers with immune disorders]. / Praktische adviezen voor reizigers met een afweerstoornis.

For patients with immune disorders, the risk of infection during travel depends on the cause and severity of the immune disorder and the type of travel. Immunocompromised travellers experience more severe effects of illness than those without immune disorders. Some risks can be reduced or avoided by taking adequate precautions and, in some cases, modifying travel plans. Ensuring adequate medication use during the trip requires careful planning prior to travel. Regarding vaccination, immunocompromised travellers may have an impaired ability to generate antibodies; live attenuated vaccines are often contraindicated. The treating physician must take a proactive role when an immunocompromised patient indicates that he or she plans to travel. Protocols developed by the Dutch National Coordination Centre for Travellers Health (LCR) provide practical advice regarding a number of situations. Provided that they are given proper individualised advice, there is little concrete evidence to suggest that these patients should not travel anywhere they wish.

[Community-acquired Staphylococcus aureus pneumonia following influenza and the choice of empirical antibiotic treatment]. / Thuis opgelopen pneumonie door Staphylococcus aureus na influenza en de keuze voor empirische antibiotische behandeling.

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 associated with high mortality and methicillin resistance, but in this patient the strain was susceptible to methicillin. The patient died. In the Netherlands the risk of methicillin resistance in PVL-positive S. aureus CAP is low but real. This should be taken into account when selecting empirical treatment, which can include the combination of flucloxacillin and rifampicin. This case report illustrates the difficulty in predicting the causative agent in CAP and highlights the usefulness of the sputum Gram stain. Moreover, clinical awareness and recognition of S. aureus CAP remains essential to the early initiation of directed therapy.

A case of delayed diagnosis of East-African trypanosomiasis in a Dutch traveller.

We present a case of East-African trypanosomiasis (EAT) in a 56-year-old Dutch woman returning from holiday in Tanzania and Kenya. The diagnosis was delayed due to the lack of suspicion and secondly because of postponed analysis of blood microscopy after negative rapid malaria antigen testing. Second stage trypanosomiasis was ruled out with liquor analysis. She was treated first with pentamidine and shortly thereafter with suramin, after which she recovered. We emphasize the use of thin/thick smear diagnostics in travellers returning from endemic countries.

The burden of Invasive Aspergillosis in patients with haematological malignancy: A meta-analysis and systematic review.

INTRODUCTION: Successful treatment of haematological malignancies is frequently complicated by Invasive Aspergillosis (IA), a life-threatening fungal infection that occurs in at least 10% of haemato-oncological patients. Case fatality rates (CFR) may fluctuate over time, depending on host pathogen interactions as well as on treatment and quality of patient care. We conducted a systematic review and metaanalysis of current - i.e. 2008-revised EORTC-MSG criteria era - incidence and case fatality rates (CFR) of IA in patients with haematological malignancy. METHODS: A systematic search according to PRISMA guidelines was performed to identify all literature reporting populations with a haematological malignancy and the incidence of IA, defined according to the EORTC/MSG 2008 criteria. Pooled cumulative incidences and CFR within 100 days were estimated using a random effects model for predefined patient populations and stratified by use of prophylaxis. RESULTS: The systematic literature search yielded 1285 publications of which n = 49 met the inclusion criteria. Overall, 16.815 patients were involved of which 1056 (6.3%) developed IA. IA risk ranged from 4% (during remission-induction, with prophylaxis) to 11% (during remission-induction, without prophylaxis). Antifungal prophylaxis was associated with a lower rate of IA, especially in the pre-HSCT population. The pooled CFR within 100 days was 29% (95% CI: 20-38%). DISCUSSION: This study confirms that IA is a relevant threat in the treatment of haematological cancer despite the universal use of antifungal prophylaxis. These outcomes inform scientists and other stakeholders about the current burden of IA and may be used to direct, implement and improve antifungal stewardship programs.