Positive Impact of [18F]FDG-PET/CT on Mortality in Patients With Staphylococcus aureus Bacteremia Explained by Immortal Time Bias.

BACKGROUND: Several studies have suggested that in patients with Staphylococcus aureus bacteremia (SAB) [18F] fluorodeoxyglucose positron emission tomography/computed tomography ([18F]FDG-PET/CT) improves outcome. However, these studies often ignored possible immortal time bias. METHODS: Prospective multicenter cohort study in 2 university and 5 non-university hospitals, including all patients with SAB. [18F]FDG-PET/CT was performed on clinical indication as part of usual care. Primary outcome was 90-day all-cause mortality. Effect of [18F]FDG-PET/CT was modeled with a Cox proportional hazards model using [18F]FDG-PET/CT as a time-varying variable and corrected for confounders for mortality (age, Charlson score, positive follow-up cultures, septic shock, and endocarditis). Secondary outcome was 90-day infection-related mortality (assessed by adjudication committee) using the same analysis. In a subgroup-analysis, we determined the effect of [18F]FDG-PET/CT in patients with high risk of metastatic infection. RESULTS: Of 476 patients, 178 (37%) underwent [18F]FDG-PET/CT. Day-90 all-cause mortality was 31% (147 patients), and infection-related mortality was 17% (83 patients). The confounder adjusted hazard ratio (aHR) for all-cause mortality was 0.50 (95% confidence interval [CI]: .34-.74) in patients that underwent [18F]FDG-PET/CT. Adjustment for immortal time bias changed the aHR to 1.00 (95% CI .68-1.48). Likewise, after correction for immortal time bias, [18F]FDG-PET/CT had no effect on infection-related mortality (cause specific aHR 1.30 [95% CI .77-2.21]), on all-cause mortality in patients with high-risk SAB (aHR 1.07 (95% CI .63-1.83) or on infection-related mortality in high-risk SAB (aHR for 1.24 [95% CI .67-2.28]). CONCLUSIONS: After adjustment for immortal time bias [18F]FDG-PET/CT was not associated with day-90 all-cause or infection-related mortality in patients with SAB.

Enteral Vancomycin to Eliminate MRSA Carriership of the Digestive Tract in Critically Ill Patients.

BACKGROUND: Carriership with methicillin resistant Staphylococcus aureus (MRSA) is a risk for the development of secondary infections in critically ill patients. Previous studies suggest that enteral vancomycin is able to eliminate enteral carriership with MRSA. Data on individual effects of this treatment are lacking. METHODS: Retrospective analysis of a database containing 15 year data of consecutive patients from a mixed medical-(cardio)surgical 18 bedded intensive care unit was conducted. All consecutive critically ill patients with enteral MRSA carriership detected in throat and/or rectal samples were collected. We analyzed those with follow-up cultures to determine the success rate of enteral vancomycin. Topical application of 2% vancomycin in a sticky oral paste was performed combined with a vancomycin solution of 500 mg four times daily in the nasogastric tube. This treatment was added to a regimen of selective digestive tract decontamination (SDD) to prevent ICU acquired infection. RESULTS: Thirteen patients were included. The mean age was 65 years and the median APACHE II score was 21. MRSA was present in the throat in 8 patients and in both throat and rectum in 5 patients. In all patients MRSA was successfully eliminated from both throat and rectum, which took 2-11 days with a median duration until decontamination of 4 days. Secondary infections with MRSA did not occur. CONCLUSIONS: Topical treatment with vancomycin in a 2% sticky oral paste four times daily in the nasogastric tube was effective in all patients in the elimination of MRSA and prevented secondary MRSA infections.

All-Cause and Infection-Related Mortality in Staphylococcus aureus Bacteremia, a Multicenter Prospective Cohort Study.

Background: Staphylococcus aureus bacteremia (SAB) is a heterogeneous disease with changing epidemiology due to changing demographics and evolving clinical management. SAB is associated with high mortality, but the current fraction of infection-related mortality is less well quantified. Methods: In a multicenter prospective cohort study of consecutive patients with SAB, we determined clinical features of SAB and determined 90-day mortality and risk factors of all-cause and infection-related mortality. Infection-related mortality was based on an adjudication committee evaluation. Results: Four hundred ninety patients with SAB were included, with community-acquired (n = 166), health care-associated (n = 163), and hospital-acquired SAB (n = 161). Endocarditis (n = 90, 18.3%), peripheral intravenous catheter infection (n = 80, 16.3%), and septic arthritis (n = 58, 11.8%) were the most frequent diagnoses, but proportions differed for community, health care, and hospital acquisition. One hundred ninety-two patients (39%) had permanent implanted prosthetic material (eg, prosthetic joint, heart valve, pacemaker). Day 90 all-cause mortality was 33% (n = 161), with 60% adjudicated as infection-related, and 90% of infection-related deaths occurring in the first 30 days post-SAB. Infection-related deaths after 30 days were rare and mainly related to endocarditis. Determinants associated with day 90 infection-related mortality were age (odds ratio [OR], 1.09; 95% CI, 1.06-1.11), Charlson comorbidity index (OR, 1.13; 95% CI, 1.01-1.26), septic shock (OR, 9.78; 95% CI, 4.56-20.95), endocarditis (OR, 3.4; 95% CI, 1.75-6.61), and persistent SAB at 48 hours (OR, 2.36; 95% CI, 1.27-4.37). Conclusions: Mortality due to S. aureus infection remains high and mainly occurs in the first 30 days, which could guide end points in future studies.

Prediction Rules for Ruling Out Endocarditis in Patients With Staphylococcus aureus Bacteremia.

BACKGROUND: Staphylococcus aureus bacteremia (SAB) is in 10% to 20% of cases complicated by infective endocarditis. Clinical prediction scores may select patients with SAB at highest risk for endocarditis, improving the diagnostic process of endocarditis. We compared the accuracy of the Prediction Of Staphylococcus aureus Infective endocarditiseTime to positivity, Iv drug use, Vascular phenomena, preExisting heart condition (POSITIVE), Predicting Risk of Endocarditis Using a Clinical Tool (PREDICT), and VIRSTA scores for classifying the likelihood of endocarditis in patients with SAB. METHODS: Between August 2017 and September 2019, we enrolled consecutive adult patients with SAB in a prospective cohort study in 7 hospitals in the Netherlands. Using the modified Duke Criteria for definite endocarditis as reference standard, sensitivity, specificity, negative predictive (NPV), and positive predictive values were determined for the POSITIVE, PREDICT, and VIRSTA scores. An NPV of at least 98% was considered safe for excluding endocarditis. RESULTS: Of 477 SAB patients enrolled, 33% had community-acquired SAB, 8% had a prosthetic valve, and 11% a cardiac implantable electronic device. Echocardiography was performed in 87% of patients, and 42% received transesophageal echocardiography (TEE). Eighty-seven (18.2%) had definite endocarditis. Sensitivity was 77.6% (65.8%-86.9%), 85.1% (75.8%-91.8%), and 98.9% (95.7%-100%) for the POSITIVE (n = 362), PREDICT, and VIRSTA scores, respectively. NPVs were 92.5% (87.9%-95.8%), 94.5% (90.7%-97.0%), and 99.3% (94.9%-100%). For the POSITIVE, PREDICT, and VIRSTA scores, 44.5%, 50.7%, and 70.9% of patients with SAB, respectively, were classified as at high risk for endocarditis. CONCLUSIONS: Only the VIRSTA score had an NPV of at least 98%, but at the expense of a high number of patients classified as high risk and thus requiring TEE. CLINICAL TRIALS REGISTRATION: Netherlands Trial Register code 6669.

[Peritoneal tuberculosis in a postmenopausal woman with progressive ascites]. / Peritoneale tuberculose.

BACKGROUND: The non-specific symptomatology in peritoneal tuberculosis often results in a delay in the diagnosis. Due to clinical overlap symptoms may be confused with metastatic ovarian carcinoma. This can lead to delayed treatment, unnecessary surgical interventions and a deteriorated prognosis. CASE DESCRIPTION: A 75-year-old female of Moroccan descent was referred to the gastroenterology department with increasing ascites and weight loss. Based on the clinical picture metastatic ovarian cancer was suspected. However, repeatedly no malignant cells were found in both ascitic fluid and tissue biopsies. Peritoneal tuberculosis was considered and ovarian malignancy could not be excluded. A diagnostic laparoscopyand biopsy was considered necessary. The laparoscopic view was pathognomic for tuberculosis after which antituberculosis treatment was started with good result. CONCLUSION: Peritoneal tuberculosis should be included in the differential diagnosis in women from endemic areas with symptoms of abdominal pain, ascites, weight loss and/or increased CA-125. Laparoscopy should be considered if less invasive tests are inconclusive about the diagnosis.

Clinical, virological and epidemiological characteristics of rhinovirus infections in early childhood: A comparison between non-hospitalised and hospitalised children.

BACKGROUND: Several studies have been published regarding the epidemiology and clinical significance of the different rhinovirus (RV) species (-A, -B and -C). However, data on RV types and the associations with clinical outcome in young children are limited. Here, we investigated the clinical, virological and epidemiological characteristics of RV infections in young children with mild or asymptomatic infection (non-hospitalised children) and in symptomatic young children admitted to the hospital. OBJECTIVES: The aim of this study was to evaluate associations between different characteristics of RV infections and clinical outcome in young children. STUDY DESIGN: RV-infected children were retrospectively selected from a Dutch birth cohort (EUROPA-study) and from hospitalised children admitted to the hospital because of respiratory symptoms. In total 120 RV-typed samples could be selected from 65 non-hospitalised and 49 hospitalised children between November 2009 and December 2012. RESULTS: RV-A was the predominant species in both study populations, followed closely by RV-C. RV-B was observed only sporadically. The distribution of the RV species was comparable in non-hospitalised and hospitalised children. In children with respiratory distress who required ICU-admission the distribution of RV species did not differ significantly from the non-hospitalised children. No predominant RV type was present in non-hospitalised nor hospitalised children. However, hospitalised children were younger, had more often an underlying illness, a higher RV load and more frequently a bacterial co-infection. CONCLUSIONS: Clinical outcome of RV infected young children was not related to RV species or types, but may more likely be influenced by multiple (host-specific) factors.

Hookworm with hypereosinophilia: atypical presentation of a typical disease.

We describe a 55-year-old man returning from the Philippines infected with a hookworm, the novel bacterium Laribacter hongkongensis, and a Blastocystis hominis and presenting with both gastrointestinal and neurological symptoms. The high eosinophilia caused by the hookworm infection resulted in both gastrointestinal and neurological symptoms, resembling a hypereosinophilic syndrome.

Febrile neutropenia: significance of elaborated screening for respiratory viruses, and the comparison of different sampling methods, in neutropenic patients with hematological malignancies.

BACKGROUND: During febrile neutropenia in only 30 to 60 percent an infectious agent is identified. This diagnostic gap could hypothetically be reduced with the broad implementation of molecular detection techniques like PCR, which has revolutionized the detection of infectious diseases during the last two decades. FINDINGS: We performed a longitudinal prospective study (N = 81) of neutropenic patients to assess the role of respiratory viruses in neutropenic fever and to determine the clinical relevance of blind screening for these viruses. Respiratory viruses were recovered in 14% of the patients prior to neutropenia. In 13% of neutropenic patients without fever and in 19% of those with fever, a respiratory virus was detected. Comparing different sample types; nasal swabs performed significantly better (16/117 = 43%), than throat swabs (6/106 = 6%). Throat gurgles did not show significant differences from the latter sample types. CONCLUSIONS: Blind diagnostic screening for respiratory viruses before or during neutropenia is not useful. Nasal swabs are sensitive and practical option for screening on respiratory viruses.

Frequent detection of respiratory viruses without symptoms: toward defining clinically relevant cutoff values.

Highly sensitive techniques, such as PCR, have greatly improved the detection of respiratory viruses. However, the sensitivity of PCR tests also complicates clinical interpretation, as the presence of small amounts of viral targets may not necessarily have clinical relevance. We performed a prospective case-control study in asymptomatic and symptomatic young children. PCR detection of 14 respiratory viruses was performed in nasal washes, and results were quantified in copies per milliliter. A total of 141 cases and 157 controls were included. In 72% of the cases and 28% of the controls, at least one virus was identified. When stratified for age, at least one virus was identified in 47% of the controls younger than 1 year old. Rhinovirus (RV) was frequently detected in both symptomatic and asymptomatic individuals. Receiver operating characteristic analysis for quantitative rhinovirus detection showed that cutoff values for clinical relevance are feasible for RV. In contrast to rhinovirus, respiratory syncytial virus (RSV) was rarely detected in controls, suggesting that a positive RSV test result is almost always of clinical relevance, independent of viral quantity. In conclusion, our study shows that asymptomatic carriage of a respiratory virus occurs frequently in young children. However, significant differences in the amount of virus present were observed between cases and controls. This suggests that defining cutoff levels should be feasible and represents the next necessary step for diagnosing viral respiratory infections using molecular tests.

Development and evaluation of a four-tube real time multiplex PCR assay covering fourteen respiratory viruses, and comparison to its corresponding single target counterparts.

BACKGROUND: Multiplex real time PCR is increasingly used to diagnose respiratory viruses and has shown to be superior to traditional methods, like culture and antigen detection. However, comprehensive data on sensitivity, specificity and performance of the multiplex PCR compared to the single target PCR's is limited for most published respiratory multiplex real time PCR assays. OBJECTIVES: Development and extensive analysis of an internally controlled multiplex real time rt-PCR for detection of respiratory viruses. STUDY DESIGN: The assay was validated in comparison to single-target PCR's using plasmid targets and prospectively collected nasopharyngeal aspirates. RESULTS: Using plasmid targets the multiplex format was found to be as least as sensitive and specific as the single-target PCR and no competition was observed when different targets were present at different amounts in one tube. Clinical validation showed high concordance for all viruses tested except for samples with low levels of enterovirus. CONCLUSION: This multiplex showed excellent specificities for all 14 respiratory viruses and sensitivity was high except for clinical samples with low levels of enterovirus.

Molecular epidemiology and evolution of human respiratory syncytial virus and human metapneumovirus.

Human respiratory syncytial virus (HRSV) and human metapneumovirus (HMPV) are ubiquitous respiratory pathogens of the Pneumovirinae subfamily of the Paramyxoviridae. Two major surface antigens are expressed by both viruses; the highly conserved fusion (F) protein, and the extremely diverse attachment (G) glycoprotein. Both viruses comprise two genetic groups, A and B. Circulation frequencies of the two genetic groups fluctuate for both viruses, giving rise to frequently observed switching of the predominantly circulating group. Nucleotide sequence data for the F and G gene regions of HRSV and HMPV variants from the UK, The Netherlands, Bangkok and data available from Genbank were used to identify clades of both viruses. Several contemporary circulating clades of HRSV and HMPV were identified by phylogenetic reconstructions. The molecular epidemiology and evolutionary dynamics of clades were modelled in parallel. Times of origin were determined and positively selected sites were identified. Sustained circulation of contemporary clades of both viruses for decades and their global dissemination demonstrated that switching of the predominant genetic group did not arise through the emergence of novel lineages each respiratory season, but through the fluctuating circulation frequencies of pre-existing lineages which undergo proliferative and eclipse phases. An abundance of sites were identified as positively selected within the G protein but not the F protein of both viruses. For HRSV, these were discordant with previously identified residues under selection, suggesting the virus can evade immune responses by generating diversity at multiple sites within linear epitopes. For both viruses, different sites were identified as positively selected between genetic groups.

Quantitation of respiratory viruses in relation to clinical course in children with acute respiratory tract infections.

Quantitation of respiratory viruses by PCR could potentially aid in clinical interpretation of PCR results. We conducted a study in children admitted with acute respiratory tract infections to study correlations between the clinical course of illness and semiquantitative detection of 14 respiratory viruses. Clinical improvement was associated with reduction of viral quantity after 3 days of hospitalization.

Azole-resistant central nervous system aspergillosis.

Three patients with central nervous system aspergillosis due to azole-resistant Aspergillus fumigatus (associated with a leucine substitution for histidine at codon 98 [L98H] and a 34-base pair repeat in tandem in the promoter region) are described. The patients were treated with combination therapy or with polyenes, but all patients died. Azole resistance significantly complicates the management of aspergillosis by delaying the initiation of adequate therapy and because effective alternative antifungal drugs are lacking.