Current clinical practice in antibiotic treatment of Staphylococcus aureus bacteraemia: results from a survey in five European countries.

OBJECTIVES: To determine clinical practice variation and identify knowledge gaps in antibiotic treatment of Staphylococcus aureus bacteraemia (SAB). METHODS: A web-based survey with questions addressing antibiotic treatment of SAB was distributed through the ESGAP network among infectious disease specialists, clinical microbiologists and internists in Croatia, France, Greece, the Netherlands and the UK between July 2021 and November 2021. RESULTS: A total number of 1687 respondents opened the survey link, of whom 677 (40%) answered at least one question. For MSSA and MRSA bacteraemia, 98% and 94% preferred initial monotherapy, respectively. In patients with SAB and non-removable infected prosthetic material, between 80% and 90% would use rifampicin as part of the treatment. For bone and joint infections, 65%-77% of respondents would consider oral step-down therapy, but for endovascular infections only 12%-32% would. Respondents recommended widely varying treatment durations for SAB with different foci of infection. Overall, 48% stated they used 18F-fluorodeoxyglucose positron emission tomography/CT (18F-FDG-PET/CT) to guide antibiotic treatment duration. Persistent bacteraemia was the only risk factor for complicated SAB that would prompt a majority to extend treatment from 2 to 4-6 weeks. CONCLUSIONS: This survey in five European countries shows considerable clinical practice variation between and within countries in the antibiotic management of SAB, in particular regarding oral step-down therapy, choice of oral antibiotic agents, treatment duration and use of 18F-FDG-PET/CT. Physicians use varying criteria for treatment decisions, as evidence from clinical trials is often lacking. These areas of practice variation could be used to prioritize future studies for further improvement of SAB care.

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.

Meta-analysis of the role of colonoscopy after an episode of left-sided acute diverticulitis.

BACKGROUND: Routine colonoscopy was traditionally recommended after acute diverticulitis to exclude coexistent malignancy. Improved CT imaging may make routine colonoscopy less required over time but most guidelines still recommend it. The aim of this review was to assess the role of colonoscopy in patients with CT-proven acute diverticulitis. METHODS: PubMed and Embase were searched for studies reporting the prevalence of advanced colorectal neoplasia (ACN) or colorectal carcinoma in patients who underwent colonoscopy within 1 year after CT-proven left-sided acute diverticulitis. The prevalence was pooled using a random-effects model and, if possible, compared with that among asymptomatic controls. RESULTS: Seventeen studies with 3296 patients were included. The pooled prevalence of ACN was 6·9 (95 per cent c.i. 5·0 to 9·4) per cent and that of colorectal carcinoma was 2·1 (1·5 to 3·1) per cent. Only two studies reported a comparison with asymptomatic controls, showing comparable risks (risk ratio 1·80, 95 per cent c.i. 0·66 to 4·96). In subgroup analysis of patients with uncomplicated acute diverticulitis, the prevalence of colorectal carcinoma was only 0·5 (0·2 to 1·2) per cent. CONCLUSION: Routine colonoscopy may be omitted in patients with uncomplicated diverticulitis if CT imaging is otherwise clear. Patients with complicated disease or ongoing symptoms should undergo colonoscopy.

A systematic review and meta-analysis of outpatient treatment for acute diverticulitis.

BACKGROUND: The shift from routine antibiotics towards omitting antibiotics for uncomplicated acute diverticulitis opens up the possibility for outpatient instead of inpatient treatment, potentially reducing the burden of one of the most common gastrointestinal diseases in the Western world. PURPOSE: Assessing the safety and cost savings of outpatient treatment in acute colonic diverticulitis. METHODS: PubMed and EMBASE were searched for studies on outpatient treatment of colonic diverticulitis, confirmed with computed tomography or ultrasound. Outcomes were readmission rate, need for emergency surgery or percutaneous abscess drainage, and healthcare costs. RESULTS: A total of 19 studies with 2303 outpatient treated patients were included. These studies predominantly excluded patients with comorbidity or immunosuppression, inability to tolerate oral intake, or lack of an adequate social network. The pooled incidence rate of readmission for outpatient treatment was 7% (95%CI 6-9%, I2 48%). Only 0.2% (2/1288) of patients underwent emergency surgery, and 0.2% (2/1082) of patients underwent percutaneous abscess drainage. Only two studies compared readmission rates outpatients that had similar characteristics as a control group of inpatients; 4.5% (3/66) and 6.3% (2/32) readmissions in outpatient groups versus 6.1% (4/66) and 0.0% (0/44) readmissions in inpatient groups (p = 0.619 and p = 0.174, respectively). Average healthcare cost savings for outpatient compared with inpatient treatment ranged between 42 and 82%. CONCLUSION: Outpatient treatment of uncomplicated diverticulitis resulted in low readmission rates and very low rates of complications. Furthermore, healthcare cost savings were substantial. Therefore, outpatient treatment of uncomplicated diverticulitis seems to be a safe option for most patients.

Risk factors for Pneumocystis jirovecii pneumonia in kidney transplant recipients and appraisal of strategies for selective use of chemoprophylaxis.

Risk stratification-based duration of trimethoprim-sulfamethoxazole (TMP-SMX) chemoprophylaxis to prevent Pneumocystis pneumonia (PCP) in kidney transplant recipients is not a universally adapted strategy and supporting evidence-based sources are limited. We performed a large retrospective study to identify risk factors for PCP in kidney transplant recipients and to define parameters for use in clinical prophylaxis guidelines. Fifty consecutive patients with confirmed PCP and 2 time-matched controls per case were enrolled. All patients were participants of the kidney transplantation program of the Leiden University Medical Center, a tertiary care hospital in the Netherlands. Potential risk factors were compared between groups by uni- and multivariate matched analyses. At transplantation, age >55 years (adjusted odds ratio [OR] 2.7, 95% confidence interval [CI] 1.3-5.9) and not receiving basiliximab induction therapy (adjusted OR 4.3, 95% CI 1.1-17.1) predicted development of PCP. In the final multivariate analysis, only cytomegalovirus infection (adjusted OR 3.0, 95% CI 1.2-7.9) and rejection treatment (adjusted OR 5.8, 95% CI 1.9-18) were found to be independently associated with PCP. Using the variables identified by the multivariate analyses, effects of different hypothetical chemoprophylaxis strategies were systematically evaluated. Exploring different scenarios showed that chemoprophylaxis in the first 6 months for all renal transplant patients - and during the first year posttransplantation for patients >55 years of age or those treated for rejection - would result in very low PCP incidence and optimal avoidance of TMP-SMX toxicity. The results provide a rationale for further prospective study on targeted provision of chemoprophylaxis to prevent PCP in kidney transplant patients.

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.

Potential influence of more-sensitive HIV-1 load detection by the new Roche Cobas AmpliPrep/Cobas TaqMan version 2.0 assay on clinical management of HIV-positive pregnant women.

With the introduction of the new Roche Cobas AmpliPrep/Cobas TaqMan version 2.0 assay, HIV-1 viral loads will be detected more frequently during the peripartum period in pregnant HIV-positive women. The implications for the clinical management of these patients are discussed in this paper.

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.

[Hydroxychloroquine and chloroquine for COVID-19: no evidence of effectiveness]. / Hydroxychloroquine en chloroquine bij COVID-19.

On 3 March 2020, the document 'Drug treatment options for patients with COVID-19 (infections with SARS-CoV-2)' was published on the website of the Dutch Working Party on Antibiotic Policy (StichtingWerkgroepAntibioticabeleid, SWAB). Based on a 7-step analysis of the literature, hydroxychloroquine (HCQ) and chloroquine (CQ) were initially included in the SWAB document as possible drug treatments for hospitalised adult COVID-19 patients. However, recent weeks have seen the publication of the results of various studies into the effectiveness of treatment with HCQ and CQ in patients with COVID-19. On the basis of these results, we conclude that there is insufficient evidence to consider HCQ and CQ as meaningful treatment options in patients with COVID-19. Clinically relevant QTc prolongation occurs in at least 1 in 10 COVID-19 patients treated with HCQ or HQ.

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.

Effects of a disinfection device on colonization of sink drains and patients during a prolonged outbreak of multidrug-resistant Pseudomonas aeruginosa in an intensive care unit.

BACKGROUND: Sink drains in intensive care units (ICUs) are frequently colonized with bacteria such as Pseudomonas aeruginosa. AIM: To study the influence of installing disinfecting devices on sink drains on colonization of sinks and patients in an ICU during a prolonged outbreak of multidrug-resistant P. aeruginosa. METHODS: From 2010, there was a clonal outbreak of multidrug-resistant P. aeruginosa (MDR-PA). In April 2013, in ICU subunit A, the siphons draining these sinks were replaced by devices applying heat and electromechanical vibration to disinfect the draining fluid. In the other units, siphons were replaced by new polyvinyl chloride plastic siphons (control). In February 2016 the disinfecting devices were also placed at ICU subunit B. FINDINGS: Baseline colonization rate of sinks was 51% in ICU A and 46% in ICU B. In ICU A colonization decreased to 5% (P < 0.001) after the intervention whereas it was 62% in ICU B (control). After installing the disinfection devices in ICU B, colonization rate was 8.0 and 2.4% in ICU A and B, respectively (both P < 0.001 compared with baseline). Colonization in ICU patients decreased from 8.3 to 0 per 1000 admitted patients (P < 0.001) and from 2.7 to 0.5 per 1000 admitted patients (P = 0.1) in ICU A and B respectively. CONCLUSION: Colonization with MDR-PA in sink drains in an ICU was effectively managed by installing disinfection devices to the siphons of sinks. Colonization of patients was also significantly reduced, suggesting that sink drains can be a source of clinical outbreaks with P. aeruginosa and that disinfecting devices may help to interrupt these outbreaks.

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.

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.

Multiflora and Gram-Negative Microorganisms Predominate in Infections Affecting Pelvic Endoprostheses Following Tumor Resection.

BACKGROUND: Periprosthetic infections after pelvic reconstruction are common, with reported rates ranging from 11% to 53%. Management of these infections is troublesome, as they commonly necessitate multiple surgical interventions and implant removal. The epidemiology and outcomes of these infections are largely unknown. The aim of this study was to analyze the causative microorganisms and the clinical outcome of treatment in a series of patients with pelvic endoprostheses affected by infection following tumor resection. METHODS: In this retrospective, multicenter cohort study, we identified all patients who developed an infection after endoprosthetic reconstruction in periacetabular tumor resection, between 2003 and 2017. The microorganisms that were isolated during the first debridement were recorded, as were the number of reoperations for ongoing infection, the antimicrobial treatment strategy, and the outcome of treatment. RESULTS: In a series of 70 patients who underwent pelvic endoprosthetic reconstruction, 18 (26%) developed an infection. The type of pelvic resection according to the Enneking-Dunham classification was type P2-3 in 14 (78%) of these patients and type P2 in 4 (22%). Median follow-up was 66 months. Fourteen (78%) of the 18 patients with infection had a polymicrobial infection. Enterobacteriaceae were identified on culture for 12 (67%). Of a total 42 times that a microorganism was isolated, the identified pathogen was gram-negative in 26 instances (62%). Microorganisms associated with intestinal flora were identified 32 times (76%). At the time of latest follow-up, 9 (50%) of the patients had the original implant in situ. Of these, 2 had a fistula and another 2 were receiving suppressive antibiotic therapy. In the remaining 9 (50%) of the patients, the original implant had been removed. At the time of final follow-up, 3 of these had a second implant in situ. The remaining 6 patients had undergone no secondary reconstruction. CONCLUSIONS: Infections that affect pelvic endoprostheses are predominantly polymicrobial and caused by gram-negative microorganisms, and may be associated with intestinal flora. This differs fundamentally from mono-bacterial gram-positive causes of conventional periprosthetic joint infections and may indicate a different pathogenesis. Our results suggest that prophylaxis and empiric treatment may need to be re-evaluated. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

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.

Meningitis caused by Capnocytophaga canimorsus: when to expect the unexpected.

In this article we review the available data concerning meningitis caused by Capnocytophaga canimorsus. The clinical presentation of this rare condition is described with the emphasis on associated conditions and management issues. Two additional cases, illustrating the difficulties in recognizing this rare disease, are presented. Reviewing a total of 28 reported cases, a preceding bite-incident by a cat or dog, or close contact with these animals, was described in the majority of cases (89%). Patients had a median age of 58 years; splenectomy and alcohol abuse were noted in, respectively, 18% and 25% of patients. Only in one case immune suppressive drug use was reported. The diagnosis C. canimorsus meningitis should be considered in healthy and immunocompromised adults, especially after splenectomy, who present with symptoms attributable to meningitis and a history of recent exposure to dogs or cats. The possibility of this condition has implications for both the diagnostic work-up and the treatment of the patient.

A new time-dependent approach for assessment of the impact of invasive aspergillosis shows effect on short- but not on long-term survival of patients with AML or high-risk MDS.

Invasive aspergillosis (IA) has been reported to yield high mortality rates. Patients with an unfavourable prognostic haematological disease not only have a higher probability of developing IA but are also more likely to die due to causes directly related to the underlying disease. This complexity of risk mechanisms confounds the causal interpretation of IA occurrence and mortality. Full consideration of the changing patient characteristics over time is necessary to obtain reliable estimates of the correlation of IA with mortality. We studied the effect of IA on mortality in 167 consecutive patients starting with remission-induction therapy for AML or of whom most patients continued to haematopoietic stem cell transplantation (HSCT). No standard antifungal prophylaxis was administered in the period before HSCT. Survival analyses were performed to determine risk estimates of IA for different phases of treatment before and after HSCT. Time-dependent adjustment for confounding variables was performed using Cox proportional hazards models. In 55 of 167 enroled patients, IA was diagnosed. Before HSCT, adjusted hazard ratios and 95% confidence intervals on mortality after the diagnosis of IA were 3.5 (1.7-7.5), 2.0 (0.69-5.9), 2.3 (0.79-6.8) and 0.80 (0.49-1.4) within 30 days, between 30 and 60 days, between 60 and 90 days or more than 90 days, respectively. A similar pattern was observed after HSCT. The occurrence of IA did not significantly influence the decision to follow through with HSCT. The results provide new insights in short- and long-term survival of patients diagnosed with IA. A significantly increased mortality risk was only observed in the first month after diagnosis of IA. No unfavourable association with mortality was observed in the later course of treatment. The occurrence of IA did not affect the probability of attaining HSCT in our population.

Helicobacter pylori resistance in the Netherlands: a growing problem?

Helicobacter pylori infection is clinically associated with dyspepsia, gastric and duodenal ulcers, and gastric cancer. Increasing antimicrobial resistance in H. pylori is a worldwide problem and failure of eradication with standard triple therapy (high-dose proton pump inhibition, amoxicillin and clarithromycin) is directly related to the presence of a resistant strain. Other treatment combinations have been investigated, but with inconsistent results. Based on a review of the recent literature in conjunction with an analysis of the regional resistance data, we address the increasing complexity of H. pylori eradication therapy. Culture and susceptibility results of all first H. pylori isolates of adults (> 18 years) seen in the Leiden University Medical Center, from January 2006 to December 2015, were analysed (n = 707). An increase in clarithromycin resistance was observed from 9.8% to 18.1% (p = 0.002) in the periods from 2006-2010 and 2011-2015, respectively. For ampicillin the resistance increased from 6.3% to 10.0% (p = 0.37), and for metronidazole from 20.7% to 23.2% (p = 0.42). The tetracycline resistance remained low at 3.2% and 2.3%, respectively. The treatment paradigm is shifting towards individualised treatment rather than a one-strategy-fits-all approach. In case of treatment failure it should be strongly considered to refer a patient for endoscopy, biopsy and culture. Thereafter, targeted antimicrobial treatment based on susceptibility results can be initiated. Furthermore, accumulating data indicate that prolongation of treatment to 14 days, as opposed to the current standard 7 day course, contributes to a higher H. pylori eradication rate.

Immune restoration disease in HIV-infected individuals receiving highly active antiretroviral therapy: clinical and immunological characteristics.

BACKGROUND: HIV-infected patients responding to HAART can show a diverse spectrum of symptoms caused by inflammatory reaction. The pathogenesis of this phenomenon, called immune restoration disease (IRD), is unclear. This study describes the spectrum of IRD and analyses the immunological and clinical parameters that could be related to its development. METHODS: In a retrospective, matched case-control study, 17 HIV-infected individuals who developed inflammatory symptoms < 12 months after initiation of HAART were included. HIV-infected controls were matched for age, gender and CDC classification. Factors included in the analysis were: CD4+ and CD8+ cell counts, deltaCD4+ and deltaCD8+, CD4/CD8 ratios, HIV-1-RNA load (VL), AVL and the number of CDC events prior to HAART. RESULTS: The median time after initiation of HAART and developing IRD (n = 17) was 72 days (range 2-319). In nine cases (53%) a mycobacterial infection was identified as the underlying cause. HAART was started at a mean CD4+ count (+/- SD) of 55 x 10(6) /l (+/- 59) and 85 x 10(6) /l (+/- 78.0) for cases and controls, respectively (p = 0.13). After initiation of HAART, the CD4+ count showed a 10.6 fold increase at the onset of IRD in the cases and a 2.7 fold increase in the controls in an equal period of time (p = 0.020). The other parameters analysed did not differ significantly between cases and controls. CONCLUSION: We conclude that the risk of developing IRD is associated with a high-fold increase in CD4+ lymphocytes. In this study, mycobacteria are the pathogens most frequently associated with IRD.