Catheter-related infections (CRIs) include catheter-associated urinary tract infections (CAUTIs) and central line-associated bloodstream infections (CLABSIs), and they are associated with high morbidity, mortality, and healthcare costs. The diagnosis of a CRI is made difficult by its non-specific symptoms. We aimed to investigate the factors influencing the plasma concentration of galectin-3 in catheter-bearing patients and to explore its potential usefulness as an index for CRIs. Circulating the concentrations of galectin-3, we measured the chemokine (C-C) motif ligand 2, procalcitonin, and C-reactive protein in 110 patients with a central catheter, in 165 patients with a urinary catheter, and in 72 control subjects. Catheter-bearing patients had higher concentrations (p < 0.001) of galectin-3 than the control group [central catheter: 19.1 (14.0–23.4) µg/L; urinary catheter: 17.1 (12.7–25.4) µg/L; control group: 6.1 (5.0–8.7) µg/L]. We identified chronic kidney disease as an independent determinant of galectin-3 concentrations in patients with a central catheter, and serum creatinine, cardiovascular disease, and number of days that the catheter was indwelling were identified as determinants in urinary catheter patients. We found that measuring galectin-3 concentrations in urinary catheter patients with a CRI was more accurate for diagnosis than the other parameters. We conclude that the measurement of galectin-3 concentration may be useful for assessing the inflammatory status of catheter-bearing patients and may contribute to the diagnosis of CRIs in those with a urinary catheter. Full article

Background: Influenza may impair respiratory exchange in the case of lower respiratory tract infections (LRTIs). Capillary blood gas (CBG) reflects arterial blood values but is a less invasive method than arterial blood sampling. We aimed to retrospectively verify the usefulness of CBG in pediatric influenza. Material and methods: CBG parameters (pH, pCO₂, pO₂, SatO₂) in laboratory confirmed influenza cases hospitalized in 2013–2020 were verified in terms of LRTI, chest X-ray (CXR) performance, radiologically confirmed pneumonia (CXR + Pneumonia), prolonged hospitalization, and intensive care transfer. A theoretical CBG-based model for CXR performance was created and the odds ratios were compared to the factual CXR performance. Results: Among 409 children (aged 13 days–17 years 3/12, median 31 months), the usefulness of CBG decreased with the age. The SatO₂ predicted the LRTI with AUC = 0.74 (95%CI: 0.62–0.86), AUC = 0.71 (0.61–0.82), and AUC = 0.602 (0.502–0.702) in children aged <6 months old (mo), 6–23 mo, 24–59 mo, respectively, while pO₂ revealed AUC = 0.73 (0.6–0.85), AUC = 0.67 (0.56–0.78), and AUC = 0.601 (0.501–0.702), respectively. The pCO₂ predicted the LRTI most precisely in children <6 months with AUC = 0.75 (0.63–0.87), yet not in older children. A high negative predictive value for CXR + Pneumonia was seen for SatO₂ < 6 mo (96.7%), SatO₂ 6–23 mo (89.6%), pO₂ < 6 mo (94.3%), pO₂ 6–23 mo (88.9%). The use of a CBG-driven CXR protocol (based on SatO₂ and pO₂) would decrease the odds of an unnecessary CXR in children <2 years old (yo) by 84.15% (74.5–90.14%) and 86.15% (66.46–94.28%), respectively. SatO₂ and pO₂ also predicted a prolonged hospitalization <6 mo AUC = 0.71 (0.59–0.83) and AUC = 0.73 (0.61–0.84), respectively, and in 6–23 mo AUC = 0.66 (0.54–0.78) and AUC = 0.63 (0.52–0.75), respectively. Conclusions: The CBG is useful mainly in children under two years, predicts the risk of LRTI, and can help exclude the risk of CXR + pneumonia. Children under six months of age represent the group that would benefit the most from CBG. A CBG-based protocol for the performance of CXR could significantly decrease the number of unnecessary CXRs. Full article

The newly developed Axis-Shield clinical chemistry heparin-binding protein (HBP) assay (Axis-Shield Diagnostics Ltd., Dundee, Scotland) can be applied to fully automated platforms. We aimed to establish a reference interval (RI) of HBP using the Axis-Shield HBP assay, and to evaluate the analytical performance of this assay. An RI was established in 212 sodium citrated plasma samples using the non-parametric method (2.5th and 97.5th percentiles). Precision, linearity, and carry-over were evaluated according to the Clinical and Laboratory Standards Institute guidelines. The RI of HBP was between 5.3 ng/mL and 171.0 ng/mL, which could be applied regardless of gender and age. Percentage coefficients of variations (%CVs) of repeatability and within-laboratory precision were 4.9% and 6.3%, respectively, for low-concentration control and 1.6% and 3.0%, respectively, for high-concentration control. The linearity was excellent (coefficient of determination (R²) = 0.99), and the carry-over rate was negligible (0.05%). This is the first study to establish an RI of HBP using the newly developed and fully automated Axis-Shield HBP assay. The Axis-Shield HBP assay showed an acceptable level of analytical performance and could be used to measure HBP concentrations effectively in routine clinical practice. Further studies are awaited to evaluate the clinical utility of HBP using this automated assay. Full article

The Coronavirus Disease 2019 (COVID-19) pandemic forced researchers to reconsider in-person assessments due to transmission risk. We conducted a pilot study to evaluate the feasibility of using the Tasso-SST (Tasso, Inc, Seattle, Washington) device for blood self-collection for use in SARS-CoV-2 antibody testing in an ongoing COVID-19 prevalence and immunity research study. 100 participants were recruited between January and March 2021 from a previously identified sub-cohort of the Cabarrus County COVID-19 Prevalence and Immunity (C3PI) Study who were under-going bimonthly COVID-19 antibody testing. Participants were given a Tasso-SST kit and asked to self-collect blood during a scheduled visit where trained laboratory personnel performed routine phlebotomy. All participants completed an after-visit survey about their experience. Overall, 70.0% of participants were able to collect an adequate sample for testing using the device. Among those with an adequate sample, there was a high concordance in results between the Tasso-SST and phlebotomy blood collection methods (Cohen’s kappa coefficient = 0.88, Interclass correlation coefficient 0.98 [0.97, 0.99], p < 0.0001). The device received a high-level (90.0%) of acceptance among all participants. Overall, the Tasso-SST could prove to be a valuable tool for seroprevalence testing. However, future studies in larger, diverse populations over longer periods may provide a better understanding of device usability and acceptance among older participants and those with comorbidities in various use scenarios. Full article

Highly active antiretroviral therapy (HAART) is currently a combination of three (less frequently four) antiretroviral drugs; these target pathways involved in various stages of HIV replication in the body. Treatment failure is a problem facing doctors and patients using HAART. The most common cause of therapeutic failure is the development of HIV drug resistance. The emergence of resistance is associated with processes involving mutation occurring in the viral genome under the influence of evolutionary factors. Sequencing reactions were performed using the AmpliSens HIV Resist-Seq. Assembly of consensus sequences from fragments obtained during sequencing was carried out using Unipro UGENE softwar. Isolate genotyping was performed using the MEGA-X software with the Neighbor-joining algorithm. According to the analysis, 72.05% of patients had at least one significant mutation associated with drug resistance for the corresponding viral subtype. HIV-1 A6 remains the predominant HIV-1 genetic variant in Russia’s Northwestern Federal District. Among samples with drug resistance mutations, in all cases, mutations associated with pharmacological resistance to two or three drug groups were found. Given the high incidence of resistance mutations in patients on ineffective ART, surveillance of HIV-1 drug resistance, in both ART-receiving and ART-naive individuals, appears necessary. A lack of vigilance and control measures may lead to the spread of primary ART-resistant HIV strains. Full article

Hepcidin regulates iron metabolism by inhibiting intestinal iron absorption and iron release from iron stores. In addition to iron overload, inflammatory conditions also up-regulate hepcidin synthesis, which may serve as an antimicrobial defense by reducing iron availability to the invading microbes. The purpose of this study is to test this hypothesis in human patients by determining serum hepcidin concentration by enzyme linked immunosorbent assay (ELISA) in healthy blood donors (n = 60) and patients hospitalized because of bacteremia (n = 50), before (day 0) and after seven days (day 7) of appropriate antibiotic treatment. Serum hepcidin was significantly increased in patients with bacteremia, both at day 0 and at day 7, compared to healthy controls. However, there was significant reduction of serum hepcidin after 7-day treatment, in concert with changes in serum C-reactive protein (CRP). The hepcidin changes were similar for both Gram-negative and Gram-positive single infection cases, while CRP was significantly reduced only in the former. In contrast to hepcidin, the levels of serum ferritin in the patients remained high after treatment, irrespective of infection type. These data confirm the stimulation of hepcidin secretion in human subjects upon different types of systemic microbial infection and suggest that hepcidin is a more sensitive and treatment-responsive acute-phase marker than ferritin in bacteremia, which needs to be explored with bigger-sized and better-matched patient cohorts. Full article

Osteoarticular infections are major disabling diseases that can occur after orthopedic implant surgery in patients. The management of these infections is very complex and painful, requiring surgical intervention in combination with long-term antibiotic treatment. Therefore, early and accurate diagnosis of the causal pathogens is essential before formulating chemotherapeutic regimens. Although culture-based microbiology remains the most common diagnosis of osteoarticular infections, its regular failure to identify the causative pathogen as well as its long-term modus operandi motivates the development of rapid, accurate, and sufficiently comprehensive bacterial species-specific diagnostics that must be easy to use by routine clinical laboratories. Based on these criteria, we reported on the feasibility of our DendrisCHIP^® technology using DendrisCHIP^®OA as an innovative molecular diagnostic method to diagnose pathogen bacteria implicated in osteoarticular infections. This technology is based on the principle of microarrays in which the hybridization signals between oligoprobes and complementary labeled DNA fragments from isolates queries a database of hybridization signatures corresponding to a list of pre-established bacteria implicated in osteoarticular infections by a decision algorithm based on machine learning methods. In this way, this technology combines the advantages of a PCR-based method and next-generation sequencing (NGS) while reducing the limitations and constraints of the two latter technologies. On the one hand, DendrisCHIP^®OA is more comprehensive than multiplex PCR tests as it is able to detect many more germs on a single sample. On the other hand, this method is not affected by the large number of nonclinically relevant bacteria or false positives that characterize NGS, as our DendrisCHIP^®OA has been designed to date to target only a subset of 20 bacteria potentially responsible for osteoarticular infections. DendrisCHIP^®OA has been compared with microbial culture on more than 300 isolates and a 40% discrepancy between the two methods was found, which could be due in part but not solely to the absence or poor identification of germs detected by microbial culture. We also demonstrated the reliability of our technology in correctly identifying bacteria in isolates by showing a convergence (i.e., same bacteria identified) with NGS superior to 55% while this convergence was only 32% between NGS and microbial culture data. Finally, we showed that our technology can provide a diagnostic result in less than one day (technically, 5 h), which is comparatively faster and less labor intensive than microbial cultures and NGS. Full article

Serological testing (immunoassay) for Helicobacter pylori (H. pylori) is widely available and inexpensive, and does not require medication modifications before testing. It can also determine the type of infection, which helps with clinical diagnosis and treatment, and guides the use of medication. However, the performance of immunoblotting for the detection of H. pylori infections in different populations has still not been fully evaluated. We performed a retrospective analysis of patients in the Health Examination Center and Outpatient Department, from November 2017 to September 2020, at Peking Union Medical College Hospital. All the subjects were tested with the ¹³C-urea breath test (¹³C-UBT) and for IgG antibodies. A total of 1678 participants, including 1377 individuals who had undergone physical examinations, were recruited. The results of the immunoassay were significantly different from those of the ¹³C-UBT for all the subjects and outpatients (p < 0.001). For the physical examinations of individuals, the agreement between the immunoassay and the ¹³C-UBT was 0.64 (95%CI: 0.59–0.68; p < 0.001), and the H. pylori immunoassay demonstrated a sensitivity and specificity of 74.24% and 90.45%, respectively, with a positive predictive value of 71.01% and negative predictive value of 91.76%. In addition, in patients with gastric mucosal atrophy or early gastric cancer, antibody typing tests can also detect infected patients with missed UBT. The prevalence of H. pylori in Beijing was 26.8%, and the serological positivity rate for H. pylori in the population of Beijing was about 31.7% (25.1% in the physical examination population). The rate of H. pylori antibody positivity among patients with allergic diseases was 73.5%, which is significantly higher than that of the non-allergic disease population (29.3%, p < 0.001). In conclusion, H. pylori antibody typing testing can be applied as a specific test in the healthy physical examination population, and the test can be performed with the remaining serum during the physical examination. Full article

Deep neck infection (DNI) is associated with morbidity and mortality. Surgical incision and drainage (I&D) of DNI abscesses are essential. Refractory abscesses require repeat I&D. Few studies have assessed the risk factors associated with repeat I&D; here, we investigated such factors. In total, 605 patients with DNI were enrolled between July 2016 and February 2022. Of these patients, 107 underwent repeat I&D. Clinical variables were assessed. On univariate analysis, a high blood sugar level (odds ratio (OR) = 1.006, p < 0.001), the involvement of at least four neck spaces (OR = 15.44, p < 0.001), and mediastinitis (OR = 1.787, p = 0.040) were significant risk factors for repeat I&D. On multivariate analysis, a high blood sugar level (OR = 1.005, p < 0.001) and the involvement of at least four neck spaces (OR = 14.79, p < 0.001) were significant independent risk factors for repeat I&D. Patients who required repeat I&D had longer hospital stays and a higher tracheostomy rate than did other patients (both p < 0.05). The pathogens did not differ between patients who did and did not require repeat surgical I&D (all p > 0.05), but the rates of pathogen non-growth from blood cultures were 19.47% (97/498) in the group without a need for repeat I&D and 0.93% (1/107) in the group with such a need (p < 0.001). DNI can be fatal; a higher blood sugar level and the involvement of at least four neck spaces were independent risk factors for repeat surgical I&D. If at least four neck spaces are involved, we recommend controlling the blood sugar level after admission. We found significant differences in the length of hospital stay and the need for tracheostomy between groups who did and did not require repeat surgical I&D. Although the pathogens did not differ between the groups, pathogen non-growth from blood cultures was less common in the group with for repeat surgical I&D than in the group without such a need. Full article

Deep neck infection (DNI) is a severe disease affecting the deep neck spaces, and is associated with an increased risk of airway obstruction. Lemierre’s syndrome (LS) refers to septic thrombophlebitis of the internal jugular vein after pharyngeal infection, and is linked with high morbidity and mortality. Both diseases begin with an oropharyngeal infection, and concurrence is possible. However, no studies have examined the risk factors associated with co-existence of LS and DNI. Accordingly, this study examined a patient population to investigate the risk factors associated with concurrent DNI and LS. We examined data from a total of 592 patients with DNI who were hospitalized between May 2016 and January 2022. Among these patients, 14 had concurrent DNI and LS. The relevant clinical variables were assessed. In a univariate analysis, C-reactive protein (odds ratio (OR) = 1.004, 95% CI: 1.000–1.009, p = 0.045), involvement of multiple spaces (OR = 23.12, 95% CI: 3.003–178.7, p = 0.002), involvement of the carotid space (OR = 179.6, 95% CI: 22.90–1409, p < 0.001), involvement of the posterior cervical space (OR = 42.60, 95% CI: 12.45–145.6, p < 0.001) and Fusobacterium necrophorum (F. necrophorum, OR = 288.0, 95% CI: 50.58–1639, p < 0.001) were significant risk factors for concurrent DNI and LS. In a multivariate analysis, involvement of the carotid space (OR = 94.37, 95% CI: 9.578–929.9, p < 0.001), that of the posterior cervical space (OR = 24.99, 95% CI: 2.888–216.3, p = 0.003), and F. necrophorum (OR = 156.6, 95% CI: 7.072–3469, p = 0.001) were significant independent risk factors for concurrent LS in patients with DNI. The length of hospitalization in patients with concurrent LS and DNI (27.57 ± 14.94 days) was significantly longer than that in patients with DNI alone (10.01 ± 8.26 days; p < 0.001), and the only pathogen found in significantly different levels between the two groups was F. necrophorum (p < 0.001). Involvement of the carotid space, that of the posterior cervical space and F. necrophorum were independent risk factors for the concurrence of DNI and LS. Patients with concurrent LS and DNI had longer hospitalization periods than patients with DNI alone. Furthermore, F. necrophorum was the only pathogen found in significantly different levels in DNI patients with versus those without LS. Full article

Deep neck infection (DNI) is a severe disease of the deep neck spaces, which has the potential for airway obstruction. Cervical necrotizing fasciitis (CNF) is a fatal infection of the diffuse soft tissues and fascia with a high mortality rate. This study investigated risk factors in patients with concurrent DNI and CNF. A total of 556 patients with DNI were included in this study between August 2016 and December 2021. Among these patients, 31 had concurrent DNI and CNF. The relevant clinical variables were assessed. In univariate analysis, age (> 60 years, odds ratio (OR) = 2.491, p = 0.014), C-reactive protein (CRP, OR = 1.007, p < 0.001), blood sugar (OR = 1.007, p < 0.001), and diabetes mellitus (DM, OR = 4.017, p < 0.001) were significant risk factors for concurrent DNI and CNF. In multivariate analysis, CRP (OR = 1.006, p < 0.001) and blood sugar (OR = 1.006, p = 0.002) were independent risk factors in patients with concurrent DNI and CNF. There were significant differences in the length of hospital stay and therapeutic management (intubation, tracheostomy, incision and drainage) between DNI patients with and without CNF (all p < 0.05). While there were no differences in pathogens between the DNI alone and concurrent DNI and CNF groups (all p > 0.05), the rate of specific pathogen non-growth from blood cultures was 16.95% (89/525) in the DNI alone group, in contrast to 0% (0/31) in the concurrent DNI and CNF group (p = 0.008). Higher CRP and blood sugar levels were independent risk factors for the concurrence of DNI and CNF. With regard to prognosis, there were significant differences in the length of hospital stay and therapeutic management between the groups with and without CNF. While there were no significant differences in pathogens (all p > 0.05), no cases in the concurrent DNI and CNF group showed specific pathogen non-growth, in contrast to 89/525 patients in the group with DNI alone. Full article

A point-of-care diagnostic for early and rapid diagnosis of scrub typhus caused by Orientia tsutsugamushi is required for prompt and proper treatment of patients presenting with undifferentiated febrile illnesses. In this study, an immunochromatographic antigen detection test kit (ICT AgTK) that targets the highly conserved O. tsutsugamushi 60 kDa GroEL chaperonin (heat shock protein 60) was developed. E. coli-derived recombinant GroEL expressed from DNA coding for the consensus sequence of 32 GroEL gene sequences extracted from the GenBank database was used to immunize rabbits and mice. Rabbit polyclonal antibodies (pAb) were used for preparing a gold-pAb conjugate, and the rGroEL-specific mouse monoclonal antibody was used as the antigen detection reagent at the ICT test line. In-house validation revealed that the ICT AgTK gave 85, 100 and 95% diagnostic sensitivity, specificity and accuracy, respectively, compared to the combined clinical features and standard IFA when tested on 40 frozen serum samples. The test kits correctly identified 10 scrub typhus samples out of 15 fresh plasma/buffy coat samples of patients with febrile illnesses. For independent laboratory validation, the ICT AgTK was sent to one provincial hospital. The ICT AgTK utilized by the hospital medical technologist correctly identified six scrub typhus samples out of 20 serum samples of patients with fever, as confirmed by specific IgM/IgG detection by IFA. The ICT AgTK is easy to perform with rapid turn-around time. It has the potential to be used as an important tool for on-site and early scrub typhus diagnosis by allowing testing of freshly collected samples (serum, plasma or buffy coat), especially in resource-limited healthcare settings. Full article

Deep neck infection (DNI) is a serious disease of deep neck spaces that can lead to morbidities and mortality. Acute epiglottitis (AE) is a severe infection of the epiglottis, which can lead to airway obstruction. However, there have been no studies of risk factors in patients with concurrent DNI and AE. This study was performed to investigate this issue. A total of 502 subjects with DNI were enrolled in the study between June 2016 and August 2021. Among these patients, 30 had concurrent DNI and AE. The relevant clinical variables were assessed. In a univariate analysis, involvement of the parapharyngeal space (OR = 21.50, 95% CI: 2.905–158.7, p < 0.001) and involvement of the submandibular space (OR = 2.064, 95% CI: 0.961–4.434, p < 0.001) were significant risk factors for concurrent DNI and AE. In a multivariate analysis, involvement of the parapharyngeal space (OR = 23.69, 95% CI: 3.187–175.4, p = 0.002) and involvement of the submandibular space (OR = 2.465, 95% CI: 1.131–5.375, p < 0.023) were independent risk factors for patients with concurrent DNI and AE. There were no differences in pathogens, therapeutic managements (tracheostomy, intubation, surgical drainage), or hospital staying period between the 30 patients with concurrent DNI and AE and the 472 patients with DNI alone (all p > 0.05). However, we believe it is significant that DNI and AE are concurrent because both DNI and AE potentially cause airway obstruction, and concurrence of these two diseases make airway protection more difficult. The infections in critical spaces may cause the coincidence of these two diseases. Involvement of the parapharyngeal space and involvement of the submandibular space were independent risk factors associated with concurrent DNI and AE. There were no differences in pathogens between the concurrent DNI and AE group and the DNI alone group. Full article

Respiratory screening assays lacking Sample Adequacy Controls (SAC) may result in inadequate sample quality and thus false negative results. The non-adequate samples might represent a significant proportion of the total performed tests, thus resulting in sub-optimal infection control measures with implications that may be critical during pandemic times. The quantitative sample adequacy threshold can be established empirically, measuring the change in the frequency of positive results, as a function of the numerical value of “sample adequacy”. Establishing a quantitative threshold for SAC requires a big number/volume of tests to be analyzed in order to have a statistically valid result. Herein, we are offering for the first time clear clinical evidence that a subset of results, which did not pass minimal sample adequacy criteria, have a significantly lower frequency of positivity compared with the “adequate” samples. Flagging these results and/or re-sampling them is a mitigation strategy, which can dramatically improve infection control measures. Full article

The emergence of multidrug resistant Gram-negative pathogens, particularly carbapenemase producers, has forced clinicians to use last line antibiotics, such as colistin. Since colistin susceptibility testing presents several challenges, this study aimed at evaluating the performance of two alternative susceptibility methods for Klebsiella pneumoniae, namely, agar dilution (AD) and MIC test strips (MTS). These approaches were compared with the reference method, broth microdilution (BMD), and provide a quantitative description for the “skipped well” (SW) phenomenon. Colistin susceptibility was evaluated by BMD and AD in parallel and triplicate, using 141 K. pneumoniae clinical isolates while MTS performance was evaluated only for a subset (n = 121). Minimum inhibitory concentration analysis revealed that a substantial part (n = 26/141; 18.4%) of the initial isolates was deemed undetermined by BMD due to the following: discordance between replicates (1.4%); presence of multiple SWs (7.8%); and the combination of both events (9.2%). Both AD and MTS revealed a high number of false-susceptible strains (“very major errors”), 37.5% and 68.8%, respectively. However, AD agreement indices were reasonably high (EA = 71.3% and CA = 94.8%). For MTS these indices were lower, in particular EA (EA = 41.7% and CA = 89.6), but the approach enabled the detection of distinct sub-populations for four isolates. In conclusion, this study provides the most comprehensive study on the performance of AD and MTS for colistin susceptibility testing in K. pneumoniae, highlighting its limitations, and stressing the importance of sample size and composition. Further, this study highlights the impact of the SW phenomenon associated with the BMD method for K. pneumoniae. Full article

Recently, the American Thoracic Society/Infectious Diseases Society of America/Centers for Disease Control and Prevention advised against performing the interferon-γ-release assay (IGRA) test for individuals with a low risk of TB, and also recommended retesting low-risk individuals with an initial positive IGRA result. However, to evaluate both sensitivity and specificity of available tests, we compared the performance of the Standard E TB-Feron (TBF) and QuantiFERON-TB Gold Plus (QFT-Plus) assays in healthcare workers (HCWs) and tuberculosis (TB) patients. We also retrospectively investigated diabetes mellitus (DM) comorbidity among the enrolled TB patients. We prospectively collected samples from 177 HCWs and 48 TB patients. The TBF and QFT-Plus tests were performed and analyzed according to the manufacturers’ instructions. We also defined IGRA results between 0.2 and 0.7 IU/mL as ‘borderline’. The agreement rate between TBF and QFT-Plus was 92.0% (207/225) with a Cohen’s kappa value of 0.77 (95% CI, 0.68–0.87). While the majority (26/31, 83.9%) of borderline TBF results were in HCWs, the majority (14/19, 73.7%) of borderline QFT-Plus results were in TB patients. Discordant results were found in 18 samples, with TBF-positive/QFT-Plus-negative or indeterminate results in 11 HCWs and seven TB patients. After resampling from 10 HCWs (seven borderline-positive and three positive results, all <1.0), six reverted to negative. The prevalence of DM comorbidity was very high (35.4%). In summary, TBF showed substantial agreement with the QFT-Plus assay but had a higher positivity rate in both HCWs and TB patients. The negative conversion rate was high (60%) among HCWs whose initial (TB Ag-nil) result was <1.0. Full article

Identification of the causative pathogen is required to optimize the effective therapy in infective endocarditis (IE). The aim of this study was to assess a 16S rDNA PCR to identify bacteria from heart valve tissues and to evaluate its usefulness as a complement to blood and removed valves cultures. A total of 266 patients diagnosed with IE from January 2015 to December 2019 were evaluated. Results between 16S rDNA PCR from heart valve tissues were compared with microbiological cultures. Blood cultures were positive in 83.5% of patients diagnosed with IE, while 39.6% and 71.8% of the evaluated heart valve samples were positive by culture and 16S rDNA PCR, respectively. For 32 (12%) patients, 16S rDNA tissue PCR provided valuable information supporting the results of blood cultures in the case of bacteria characteristic from the skin microbiota. Additionally, a microorganism was identified by using 16S rDNA PCR in 36% of blood culture-negative cases. The present study reveals that molecular diagnosis using 16S rDNA tissue PCR provides complementary information for the diagnosis of IE, and it should be recommended in surgical endocarditis, especially when blood cultures are negative. Full article

Dental caries are one of the chronic diseases caused by organic acids made from oral microbes. However, there was a lack of knowledge about the oral microbiome of Korean children. The aim of this study was to analyze the metagenome data of the oral microbiome obtained from Korean children and to discover bacteria highly related to dental caries with machine learning models. Saliva and plaque samples from 120 Korean children aged below 12 years were collected. Bacterial composition was identified using Illumina HiSeq sequencing based on the V3–V4 hypervariable region of the 16S rRNA gene. Ten major genera accounted for approximately 70% of the samples on average, including Streptococcus, Neisseria, Corynebacterium, and Fusobacterium. Differential abundant analyses revealed that Scardovia wiggsiae and Leptotrichia wadei were enriched in the caries samples, while Neisseria oralis was abundant in the non-caries samples of children aged below 6 years. The caries and non-caries samples of children aged 6–12 years were enriched in Streptococcus mutans and Corynebacterium durum, respectively. The machine learning models based on these differentially enriched taxa showed accuracies of up to 83%. These results confirmed significant alterations in the oral microbiome according to dental caries and age, and these differences can be used as diagnostic biomarkers. Full article

SARS-CoV-2 outbreak led to unprecedented innovative scientific research to preclude the virus dissemination and limit its impact on life expectancy. Waiting for the collective immunity by vaccination, mass-testing, and isolation of positive cases remain essential. The development of a diagnosis method requiring a simple and non-invasive sampling with a quick and low-cost approach is on demand. We hypothesized that the combination of saliva specimens with MALDI-TOF MS profiling analyses could be the winning duo. Before characterizing MS saliva signatures associated with SARS-CoV-2 infection, optimization and standardization of sample collection, preparation and storage up to MS analyses appeared compulsory. In this view, successive experiments were performed on saliva from healthy healthcare workers. Specimen sampling with a roll cotton of Salivette^® devices appeared the most appropriate collection mode. Saliva protein precipitation with organic buffers did not improved MS spectra profiles compared to a direct loading of samples mixed with acetonitrile/formic acid buffer onto MS plate. The assessment of sample storage conditions and duration revealed that saliva should be stored on ice until MS analysis, which should occur on the day of sampling. Kinetic collection of saliva highlighted reproducibility of saliva MS profiles over four successive days and also at two-week intervals. The intra-individual stability of saliva MS profiles should be a key factor in the future investigation for biomarkers associated with SARS-CoV-2 infection. However, the singularity of MS profiles between individuals will require the development of sophisticated bio-statistical analyses such as machine learning approaches. MALDI-TOF MS profiling of saliva could be a promising PCR-free tool for SARS-CoV-2 screening. Full article

Millions of people are tested for COVID-19 daily during the pandemic, and a lack of evidence to guide optimal nasal swab testing can increase the risk of false-negative test results. This study aimed to determine the optimal insertion depth for nasal mid-turbinate and nasopharyngeal swabs. The measurements were made with a flexible endoscope during the collection of clinical specimens with a nasopharyngeal swab at a public COVID-19 test center in Copenhagen, Denmark. Participants were volunteer adults undergoing a nasopharyngeal SARS-CoV-2 rapid antigen test. All 109 participants (100%) completed the endoscopic measurements; 52 (48%) women; 103 (94%) white; mean age 34.39 (SD, 13.2) years; and mean height 176.7 (SD, 9.29) cm. The mean swab length to the posterior nasopharyngeal wall was 9.40 (SD, 0.64) cm. The mean endoscopic distance to the anterior and posterior end of the inferior turbinate was 1.95 (SD, 0.61) cm and 6.39 (SD, 0.62) cm, respectively. The mean depth to nasal mid-turbinate was calculated as 4.17 (SD, 0.48) cm. The optimal depths of insertion for nasal mid-turbinate swabs are underestimated in current guidelines compared with our findings. This study provides clinical evidence to guide the performance of anatomically correct nasal and nasopharyngeal swab specimen collection for virus testing. Full article

Conventional methods for etiologic diagnoses of acute gastroenteritis (AGE) are time consuming and have low positive yield leading to limited clinical value. This study aimed to investigate quality improvements in patient management, antibiotic stewardship, and in-hospital infection transmission prevention using BioFire^® FilmArray^® Gastrointestinal Panel (GI Panel) in children with acute diarrhea. This was a prospective study recruiting children < 19 years old with new onset diarrhea during the study period, and a matched historical cohort study of children diagnosed with AGE during the 4 years prior. Patients in the prospective cohort underwent stool testing with GI Panel and conventional methods. A total of 182 patients were included in the prospective cohort, of which 85.7% (n = 156) had community-onset and 14.3% (n = 26) had hospital-onset diarrhea. A higher pathogen positivity rate for community-onset diarrhea was observed by the GI Panel (58.3%, n = 91) compared to conventional studies (42.3%, n = 66) (p = 0.005) and historical cohort (31.4%, n = 49) (p < 0.001). The stool tests reporting time after admission was 25 (interquartile range, IQR 17–46) hours for the GI Panel, and 72 (IQR 48–96) hours for the historical cohort (p < 0.001). A significant reduction in antibiotic use was observed in the prospective cohort compared to historical cohort, 35.3% vs. 71.8%; p < 0.001), respectively. Compared to the GI Panel, norovirus ICT was only able to detect 4/11 (36.4%) patients with hospital-onset and 14/27 (51.8%) patients with community-onset diarrhea. The high positivity rate and rapid reporting time of the GI Panel had clinical benefits for children admitted for acute diarrhea, especially by reducing antibiotic use and enabling early adequate infection precaution and isolation. Full article

Accurate and early prediction of poststroke infections is important to improve antibiotic therapy guidance and/or to avoid unnecessary antibiotic treatment. We hypothesized that the combination of blood biomarkers with clinical parameters could help to optimize risk stratification during hospitalization. In this prospective observational study, blood samples of 283 ischemic stroke patients were collected at hospital admission within 72 h from symptom onset. Among the 283 included patients, 60 developed an infection during the first five days of hospitalization. Performance predictions of blood biomarkers (Serum Amyloid-A (SAA), C-reactive protein, procalcitonin (CRP), white blood cells (WBC), creatinine) and clinical parameters (National Institutes of Health Stroke Scale (NIHSS), age, temperature) for the detection of poststroke infection were evaluated individually using receiver operating characteristics curves. Three machine learning techniques were used for creating panels: Associative Rules Mining, Decision Trees and an internal iterative-threshold based method called PanelomiX. The PanelomiX algorithm showed stable performance when applied to two representative subgroups obtained as splits of the main subgroup. The panel including SAA, WBC and NIHSS had a sensitivity of 97% and a specificity of 45% to identify patients who did not develop an infection. Therefore, it could be used at hospital admission to avoid unnecessary antibiotic (AB) treatment in around half of the patients, and consequently, to reduce AB resistance. Full article

There have been few reports on the kinetics of hemodialyzed (HD) patients’ immune responses in latent tuberculosis infection (LTBI). Therefore, in the present study, messenger ribonucleic acid (mRNA) expression levels of nine immune markers were analyzed to discriminate between HD patients with LTBI and healthy individuals. Nine cytokines and chemokines were screened through relative mRNA expression levels in whole blood samples after stimulation with Mycobacterium tuberculosis (MTB)-specific antigens from HD patients with LTBI (HD/LTBI), HD patients without LTBI, and healthy individuals, and results were compared with the QuantiFERON-TB Gold In-Tube (QFT-GIT) test. We confirmed that the C-C motif chemokine 11 (CCL11) mRNA expression level of the HD/LTBI group was significantly higher than the other two groups. Especially, the CCL11 mRNA expression level of the >0.7 IU/mL group in the QFT-GIT test was significantly higher than the <0.2 IU/mL group in the QFT-GIT test and the 0.2–0.7 IU/mL group in the QFT-GIT test (p = 0.0043). The present study reveals that the relative mRNA expression of CCL11 was statistically different in LTBI based on the current cut-off value (i.e., ≥0.35 IU/mL) and in the >0.7 IU/mL group. These results suggest that CCL11 mRNA expression might be an alternative biomarker for LTBI diagnosis in HD patients. Full article

Primary infection occurs when seronegative women are infected by human cytomegalovirus (HCMV). Diagnosis of primary infection is based on the following: antibody seroconversion, presence of IgM and low IgG avidity index (AI), and presence of DNAemia. The kinetics of HCMV-specific IgM antibody and maturation of AI might be very rapid or long-lasting during primary infection, which makes serological diagnosis insidious. The aims of this study were as follows: (i) to report atypical kinetics of HCMV-specific IgM antibody and AI early after onset of primary HCMV infection in a population of pregnant women, and (ii) to assess the frequency of such results. Altogether, 1309 sequential serum samples collected from 465 pregnant women with primary HCMV infection were included in the study. As a general rule, using the LIAISON^®CMVIgMII and LIAISON^®CMVIgGAvidityII assays, virus-specific IgM antibody levels decreased, while IgG AI increased over time during the first three months after infection onset. However, early clearance of IgM antibody and/or early IgG AI maturation occurred in 46/426 (10.7%) women. In more details, 20/426 (4.7%) and 26/418 (6.2%) women had undetectable IgM antibody or high IgG AI, respectively, when tested within 1–3 months after well-defined infection onset. Twenty sera from as many women with high IgG AI by the LIAISON assay were further tested for IgG AI by VIDAS^®CMVIgGAvidityII and Mikrogen recomLineCMVIgG Avidity assays. Comparable results were obtained with VIDAS, whereas 14/20 sera gave low AI with the Mikrogen assay. In conclusion, about 11% of pregnant women undergoing a primary HCMV infection showed misleading serological results. Additional and appropriate testing might help in reducing the risk of missing HCMV primary infection in pregnancy. Furthermore, preconceptional testing should be strongly recommended. Full article

The aim of the present study is to re-evaluate the clinical application of two-times serologic immunoglobulin M (IgM) tests using microparticle agglutination assay (MAA), an enzyme-linked immunosorbent assay (ELISA), and polymerase chain reaction (PCR) assay in diagnosing Mycoplasma pneumoniae (MP) infection. A retrospective analysis of 62 children with MP pneumonia during a recent epidemic (2019–2020) was conducted. The MAA and ELISA immunoglobulin M (IgM) and IgG measurements were conducted twice at admission and around discharge, and MP PCR once at presentation. Diagnostic rates in each test were calculated at presentation and at discharge. The seroconverters were 39% (24/62) of patients tested by MAA and 29% (18/62) by ELISA. At presentation, the diagnostic positive rates of MAA, ELISA, and PCR tests were 61%, 71%, and 52%, respectively. After the second examination, the rates were 100% in both serologic tests. There were positive correlations between the titers of MAA and the IgM values of ELISA. The single serologic IgM or PCR tests had limitations to select patients infected with MP in the early stage. The short-term, paired IgM serologic tests during hospitalization can reduce patient-selection bias in MP infection studies. Full article

Bacterial vaginosis (BV) affects one-third of reproductive age women, increasing the risk of acquiring sexually transmitted infections (STIs) and posing a risk for reproductive health. The current diagnosis with Gram stain (Nugent Score) identifies a transitional stage named partial BV or intermediate microbiota, raising the problem of how to clinically handle it. We retrospectively analyzed cervicovaginal swabs from 985 immunocompetent non-pregnant symptomaticspp. women (vaginal discharge, burning, itching) by Nugent score and qPCR for BV, aerobic or fungal vaginitis, and STIs (Mycoplasmas spp., Chlamydia t., Trichomonas v., and Neisseria g.). Nugent scores 0–3 and 7–10 were confirmed in 99.3% and 89.7% cases, respectively, by qPCR. Among Nugent scores 4–6 (partial BV), qPCR identified 46.1% of BV cases, with 37.3% of cases negative for BV, and only 16.7% of partial BV. Gram staining and qPCR were discordant (p value = 0.0001) mainly in the partial BV. Among the qPCR BV cases, the presence of aerobic vaginitis and STIs was identified, with a significant association (p < 0.0001) between the STIs and partial BV/overt BV. qPCR is more informative and accurate, and its use as an alternative or in combination with Gram staining could help clinicians in having an overview of the complex vaginal microbiota and in the interpretation of partial BV that can correspond to vaginitis and/or STIs. Full article

Serological diagnosis of pertussis is mainly based on anti-pertussis toxin (PT) IgG antibodies. Since PT is included in all acellular vaccines (ACV), serological assays do not differentiate antibodies induced by ACVs and infection. Adenylate cyclase toxin (ACT) is not included in the ACVs, which makes it a promising candidate for pertussis serology with the specific aim of separating infection- and ACV-induced antibodies. A multiplex lateral flow test with PT and ACT antigens was developed to measure serum antibodies from pertussis-seropositive patients (n = 46), healthy controls (n = 102), and subjects who received a booster dose of ACV containing PT, filamentous hemagglutinin, and pertactin (n = 67) with paired sera collected before and one month after the vaccination. If the diagnosis was solely based on anti-PT antibodies, 98.5–44.8% specificity (before and after vaccination, respectively) and 78.2% sensitivity were achieved, whereas if ACT was used in combination with PT, the sensitivity of the assay increased to 91.3% without compromising specificity. No increase in the level of anti-ACT antibodies was found after vaccination. This exploratory study indicates that the use of ACT for serology would be beneficial in combination with a lower quantitative cutoff for anti-PT antibodies, and particularly in children and adolescents who frequently receive booster vaccinations. Full article

The scope of dentistry is ever-changing and dynamic in all fields of dentistry including periodontal health and disease. Recent studies show that oral health and systemic health are interdependent, particularly in the way that poor oral hygiene and periodontal health affect the systemic health of an individual and vice versa. Periodontal diseases are multifactorial in nature in which the role of bacterial infections is inevitable. Furthermore, high-throughput sequencing technologies have shed light on the dysregulation of the growth of oral microbial flora and their environment, including those that are associated with periodontitis and other oral and non-oral diseases. Under such circumstances, it becomes important to explore oral microbiota and understand the effects of periodontal pathogens in the pathogenesis of systemic diseases. In addition, it may strengthen our view that a better understanding of oral microbial flora and proper examination of the oral cavity may aid in the early diagnosis and possible treatment of systemic diseases and conditions. This will eventually lead to providing better care to our patients. Therefore, in this research, we attempt to outline the periodontal pathophysiology along with the role of periodontal pathogens in some commonly encountered systemic conditions. Full article

The CRISPR/Cas system is a protective adaptive immune system against attacks from foreign mobile genetic elements. Since the discovery of the excellent target-specific sequence recognition ability of the CRISPR/Cas system, the CRISPR/Cas system has shown excellent performance in the development of pathogen nucleic-acid-detection technology. In combination with various biosensing technologies, researchers have made many rapid, convenient, and feasible innovations in pathogen nucleic-acid-detection technology. With an in-depth understanding and development of the CRISPR/Cas system, it is no longer limited to CRISPR/Cas9, CRISPR/Cas12, and other systems that had been widely used in the past; other CRISPR/Cas families are designed for nucleic acid detection. We summarized the application of CRISPR/Cas-related technology in infectious-disease detection and its development in SARS-CoV-2 detection. Full article

This article summarizes and systematizes the available data from the literature on chronic autoimmune gastritis (CAG) in order to increase the awareness of specialists about the modern possibilities for diagnosing the disease, including its early stages. The clinical manifestation of the disease includes possible variants such as gastrointestinal, hematological (first of all, the formation of iron deficiency and B12-deficiency anemia), and neurological variants. Patients with chronic autoimmune gastritis are characterized by comorbidity with other autoimmune diseases. In this paper, data on the most informative serological markers for the diagnosis of CAG, as well as laboratory tests to detect micronutrient deficiencies, information on the characteristic changes in the gastric mucosa, and the prognosis of the disease, are presented. The diagnosis of CAG should be based on a multidisciplinary approach that combines a thorough analysis of a patient’s complaints with a mandatory assessment of nutritional status, as well as the results of serological, endoscopic, and histological research methods. Full article

Convalescent plasma (CP) from patients recovered from COVID-19 is one of the most studied anti-viral therapies against SARS-COV-2 infection. The aim of this study is to summarize the evidence from the available systematic reviews on the efficacy and safety of CP in COVID-19 through an overview of the published systematic reviews (SRs). A systematic literature search was conducted up to August 2021 in Embase, PubMed, Web of Science, Cochrane and Medrxiv databases to identify systematic reviews focusing on CP use in COVID-19. Two review authors independently evaluated reviews for inclusion, extracted data and assessed quality of evidence using AMSTAR (A Measurement Tool to Assess Reviews) and GRADE tools. The following outcomes were analyzed: mortality, viral clearance, clinical improvement, length of hospital stay, adverse reactions. In addition, where possible, subgroup analyses were performed according to study design (e.g., RCTs vs. non-RCTs), CP neutralizing antibody titer and timing of administration, and disease severity. The methodological quality of included studies was assessed using the checklist for systematic reviews AMSTAR-2 and the GRADE assessment. Overall, 29 SRs met the inclusion criteria based on 53 unique primary studies (17 RCT and 36 non-RCT). Limitations to the methodological quality of reviews most commonly related to absence of a protocol (11/29) and funding sources of primary studies (27/29). Of the 89 analyses on which GRADE judgements were made, effect estimates were judged to be of high/moderate certainty in four analyses, moderate in 38, low in 38, very low in nine. Despite the variability in the certainty of the evidence, mostly related to the risk of bias and inconsistency, the results of this umbrella review highlight a mortality reduction in CP over standard therapy when administered early and at high titer, without increased adverse reactions. Full article

The high prevalence of Helicobacter pylori and the variety of gastroduodenal diseases caused by this pathogen necessitate the use of only accurate methods both for the primary diagnosis and for monitoring the eradication effectiveness. There is a broad spectrum of diagnostic methods available for detecting H. pylori. All methods can be classified as invasive or non-invasive. The need for upper endoscopy, different clinical circumstances, sensitivity and specificity, and accessibility defines the method chosen. This article reviews the advantages and disadvantages of the current options and novel developments in diagnostic tests for H. pylori detection. The progress in endoscopic modalities has made it possible not only to diagnose precancerous lesions and early gastric cancer but also to predict H. pylori infection in real time. The contribution of novel endoscopic evaluation technologies in the diagnosis of H. pylori such as visual endoscopy using blue laser imaging (BLI), linked color imaging (LCI), and magnifying endoscopy is discussed. Recent studies have demonstrated the capability of artificial intelligence to predict H. pylori status based on endoscopic images. Non-invasive diagnostic tests such as the urea breathing test and stool antigen test are recommended for primary diagnosis of H. pylori infection. Serology can be used for initial screening and epidemiological studies. The histology showed its value in detecting H. pylori and provided more information about the degree of gastric mucosa inflammation and precancerous lesions. Molecular methods are mainly used in detecting antibiotic resistance of H. pylori. Cultures from gastric biopsies are the gold standard and recommended for antibiotic susceptibility tests. Full article

Urinary tract infection (UTI) represents the most common infection after kidney transplantation and remains a major cause of morbidity and mortality in kidney transplant (KT) recipients, with a potential impact on graft survival. UTIs after KT are usually caused by Gram-negative microorganisms. Other pathogens which are uncommon in the general population should be considered in KT patients, especially BK virus since an early diagnosis is necessary to improve the prognosis. UTIs following kidney transplantation are classified into acute simple cystitis, acute pyelonephritis/complicated UTI, and recurrent UTI, due to their different clinical presentation, prognosis, and management. Asymptomatic bacteriuria (ASB) represents a frequent finding after kidney transplantation, but ASB is considered to be a separate entity apart from UTI since it is not necessarily a disease state. In fact, current guidelines do not recommend routine screening and treatment of ASB in KT patients, since a beneficial effect has not been shown. Harmful effects such as the development of multidrug-resistant (MDR) bacteria and a higher incidence of Clostridium difficile diarrhea have been associated with the antibiotic treatment of ASB. Full article

Klebsiella pneumoniae is a rod-shaped, encapsulated, Gram-negative bacteria associated with multiple nosocomial infections. Multidrug-resistant (MDR) K. pneumoniae strains have been increasing and the therapeutic options are increasingly limited. Colistin is a long-used, polycationic, heptapeptide that has regained attention due to its activity against Gram-negative bacteria, including the MDR K. pneumoniae strains. However, this antibiotic has a complex mode of action that is still under research along with numerous side-effects. The acquisition of colistin resistance is mainly associated with alteration of lipid A net charge through the addition of cationic groups synthesized by the gene products of a multi-genic regulatory network. Besides mutations in these chromosomal genes, colistin resistance can also be achieved through the acquisition of plasmid-encoded genes. Nevertheless, the diversity of molecular markers for colistin resistance along with some adverse colistin properties compromises the reliability of colistin-resistance monitorization methods. The present review is focused on the colistin action and molecular resistance mechanisms, along with specific limitations on drug susceptibility testing for K. pneumoniae. Full article

We reviewed the evidence on features of central nervous system (CNS) involvement in trichinellosis, systematically searching five databases (to January 2021). We categorized clinical features based on their diagnostic value as warning signs for severe CNS infection (with outcome death) or non-specific signs (outcome improvement). They were suggestive of severe infection if they substantially raised death probability. The review included 87 papers published from 1906 through 2019, with data on 168 patients. Mydriasis, paraparesis, dysphagia, psychomotor seizures, or delirium present a 30–45% increased death likelihood. The best poor prognosis predictor is mydriasis (positive likelihood ratio 9.08). Slow/absent light reflex, diminished/absent knee reflexes, globally decreased tendon reflexes present a moderate increase (20–25%) of death risk. Anisocoria, acalculia, or seizures could also indicate an increased death risk. We provided a detailed presentation of clinical and paraclinical signs that alert physicians of a possible neurotrichinellosis, emphasizing signs that might indicate a poor prognosis. Full article

Visceral leishmaniasis remains a serious public health issue, and Brazil was among the seven countries with the highest prevalence of this disease worldwide. The measures to control this disease are not easily developed, and the improvement of its diagnosis, surveillance, and control is still needed. This study aimed to carry out the polymerase chain reaction (PCR) diagnosis of Leishmania infantum in vector samples in some municipalities of the State of São Paulo, which included two municipalities with human disease transmission and two with dog transmission only. Vectors were collected in traps with luminous bait. Next, they were killed at −4 °C and kept in 70% alcohol. Groups of ten female insects (pools) were mashed on cation exchange paper (fine cellulose phosphate with 18 µEq/cm² ionic exchange capacity) for DNA extraction. The PCR was carried out to identify the natural infection of the Leishmania genus in female Lutzomyia longipalpis (Lu. Longipalpis). Out of the 3,880 Lu. longipalpis phlebotomines, 1060 were female and 2820 were male (3:1). The method used to extract the DNA in pools of ten phlebotomines and the PCR resulted in sensitivity, specificity, practicality, and faster analyses when compared to the individual analysis method. The procedure described can be used on a large scale in the leishmaniasis epidemiological surveillance, enabling a higher number of analyses and the optimization of human resources because the traditional diagnostic method is carried out via desiccation of the insect digestive system and microscopic examination, which is time-demanding and there is the need of manual skills. Full article

Ureaplasma parvum is usually part of the normal genital microbiota. Rarely, it can cause invasive infections such as septic arthritis or meningitis. A case of a 74-year-old woman with follicular lymphoma who developed cellulitis followed by elbow arthritis with negative routine bacterial cultures is described. U. parvum was identified in the synovial fluid using a broad-range 16S ribosomal RNA gene polymerase chain reaction (PCR) and also in vaginal fluid by a targeted PCR (Anyplex™ II STI-7). Multilocus Sequence Typing (MLST) revealed that isolates from both sources belonged to ST4, a worldwide distributed clone. Treatment consisted of surgery and targeted antibiotic therapy with doxycycline and azithromycin. Evolution showed initial clinical improvement in arthritis despite functional sequelae. Ureaplasma arthritis should be considered as a rare cause of arthritis in negative culture, especially in immunosuppressed patients. In these cases, the treatment is not well established, but according to this and previous works, patients could improve with doxycycline, azithromycin or fluoroquinolone therapy on a prolonged basis. Full article

Infectious diseases are associated with a high morbidity and mortality rate among pediatric cancer patients undergoing treatment or receiving a transplant. Neutropenia represents a potentially fatal complication of cancer treatment and is associated with a high risk of developing bacterial infections. Although febrile neutropenia (FN) can affect both adults and children, the latter has a higher chance of infections with an unknown origin. Prompt empiric broad-spectrum antibiotic administration is collectively considered the best therapeutic approach. This review aims to analyze the latest works from the literature regarding the therapeutic strategies, schemes, and approaches and the efficacy of these in pediatric febrile neutropenia. Following PRISMA guidelines, an advanced search on PubMed, Scopus, and Cochrane Library, using the keywords “febrile neutropenia”, “pediatric”, “cancer”, and “oncology”, was performed. A total of 197 articles were found to be eligible. After screening the abstracts and excluding unfit studies, 16 articles were analyzed. There were eight retrospective studies, five prospective studies, and two clinical trials. Altogether, these studies have described around 5000 episodes of FN. The median age of the participants was 7.6 years, and the underlying condition for most of them was acute leukemia. The infectious agent could only be determined in around one-fifth of cases, from which 90% were of bacterial origin. As such, empirical broad-spectrum antibiotics are used, with the most used treatment scheme comprising third- and fourth-generation cephalosporins and antipseudomonal penicillins. In order to improve the treatment strategies of FN episodes and to successfully de-escalate treatments toward narrower-spectrum antibiotics, hospitals and clinics should increase their efforts in identifying the underlying cause of FN episodes through blood culture urine culture and viral tests, wherever infrastructure enables it. Full article

Background. Ivermectin has received particular attention as a potential treatment for COVID-19. However, the evidence to support its clinical efficacy is controversial. Objectives. We undertook a new systematic review of ivermectin for the treatment and prophylaxis of COVID-19, including new primary studies, outcomes other than mortality, and grading the quality of the available evidence following the Cochrane guidance for methodology. Methods. We searched electronic databases, repository databases, and clinical trial registries (up to June 2021). The measure of treatment effect was risk difference (RD) with 95% confidence intervals (CIs). The GRADE system was used to assess the certainty of the evidence. Results. The review includes 11 RCTs (2436 participants). The certainty of the available evidence was quite low or very low due to risk of bias, inconsistency, and imprecision. When the analysis was limited to patients with baseline mild or moderate disease (8 reports, 1283 patients), there were no differences in mortality between ivermectin and control groups (low level of certainty); in patients with baseline severe diseases (3 reports, 304 patients), the use of ivermectin significantly decreased mortality compared to the controls (RD −0.17; 95% CIs, −0.24/−0.10; p = 0.00001; low level of certainty). In terms of disease progression (to severe pneumonia, admission to intensive care unit, and/or mechanical ventilation), the results were much the same. At day 14, the rate of patients with a negative RT-PCR test was 21% higher (from 5 to 36% higher) for ivermectin recipients than it was for the controls (low quality of evidence). Three studies (736 subjects) indicated that prophylaxis with ivermectin increased the likelihood of preventing COVID-19 compared to controls (low quality of evidence). Serious adverse events were rarely reported. Conclusions. There is limited evidence for the benefit of ivermectin for COVID-19 treatment and prophylaxis, and most of this evidence is of low quality. Further evidence is needed to fine-tune potential indications and optimal treatment protocols for ivermectin as a treatment for COVID-19. Full article

Histoplasmosis is a well-known endemic fungal infection but experience in non-endemic regions is often limited, which may lead to delayed diagnosis and extensive testing. The diagnosis can be especially challenging, typically when the disease first presents with pulmonary nodules accompanied by hilar and mediastinal lymphadenopathy, suggesting a much more common malignant disease. In this situation, a greater FDG uptake in draining lymph nodes in comparison with the associated lung nodule seen in [¹⁸F]FDG-PET/CT, the so-called “flip-flop fungus” sign, can help to orientate further diagnostic measures. We report a case of a 56-year-old woman living in Switzerland, a non-endemic region, whose diagnosis of imported histoplasmosis was delayed since the findings had been initially misinterpreted as pulmonary malignancy. Further, histological workup was inconclusive due to lack of specific fungal staining, leading to ineffective treatment and non-resolving disease. This paper intends to highlight the pitfalls in diagnosing Histoplasma capsulatum and presents images of particularities of fungal infections in [¹⁸F]FDG-PET/CT, which in our case showed a “flip-flop fungus” sign. Full article