Routine Infectious Diseases Consultations on a Pediatric Cardiac Unit to Improve Positive Blood Culture Management.

Bacteremia can be life-threatening, and highly medicalized patients, such as those with complex congenital heart disease, are at high risk. Infectious diseases (ID) consultation is associated with improved outcomes in bacteremia. We noted an opportunity for improvement in management of positive blood cultures in our cardiac care unit (CCU). We completed a quality improvement project that included a single plan-do-study-act cycle consisting of a policy of routine ID consultation for all positive blood cultures events in the CCU. Our outcome measure of interest was percentage of appropriately managed blood culture events, the process measure was percentage of blood culture events for which the ID service was formally consulted, and the balancing measure was number of individual patients for whom the ID service was formally consulted. Appropriate antimicrobial management was determined via chart review by an ID physician. Data were analyzed via run chart and simple statistics. Following the intervention, the rate of appropriately managed positive blood culture events increased from a baseline of 86% to 98%, and the rate of ID consultation for these events increased from 75% to 98%. A shift was noted in run charts for both the outcome and process measures. There was an increase in patients for whom the ID service was consulted throughout the entire study period. We successfully implemented mandatory ID consultations in a CCU to increase proportion of appropriately managed blood cultures. While this intervention cannot be universally applied, others may find it useful in selected scenarios.

Impact of Catheter-Drawn Blood Cultures on Patient Management: A Multicenter, Retrospective Cohort Study.

Background: Nosocomial bloodstream infections associated with intravascular catheters pose significant financial burden, morbidity, and mortality. There is much debate about whether or not blood cultures should be drawn through central venous catheters, and while guidelines advocate for catheter-drawn cultures when catheter infection is suspected, there is variable practice in this regard. Methods: We performed a retrospective cohort study assessing episodes of positive catheter-drawn blood cultures with concomitant negative percutaneously-drawn cultures in tertiary care hospitals in the United States and Spain. Results: We identified 143 episodes in 122 patients meeting inclusion criteria. Thirty percent of such episodes revealed growth of potential pathogens such as Staphylococcus aureus. Overall, 21% of follow-up percutaneously-drawn blood cultures obtained within 48 hours revealed growth of the same microbe after an episode of positive catheter-drawn blood cultures with negative concomitant percutaneously-drawn cultures (33% when potential pathogens were isolated; 16% when common skin contaminants were isolated). Patients with cultures growing pathogenic organisms were more likely to receive targeted antimicrobial therapy and have their catheters removed sooner. Conclusions: Many episodes of positive catheter-drawn blood cultures with concomitant negative percutaneously-drawn cultures lead to growth from percutaneously-drawn follow-up blood cultures. Thus, such initial discordant results should not be disregarded. Our findings advocate for a nuanced approach to blood culture interpretation, emphasizing the value of catheter-drawn blood cultures in clinical decision making and management.

Is It Useful to Repeat Blood Cultures in Endocarditis Patients? A Critical Appraisal.

BACKGROUND: Previous guidelines for endocarditis have suggested repeating blood cultures until they become negative, with limited evidence. METHODS: Literature reviews were conducted (1) on the incidence of persistent bacteremia and association with outcome and (2) on timing of valve culture negativization to examine the claim for prolongation of antibiotic therapy starting from negative blood cultures. RESULTS: Persistent bacteremia and fever may be present in the first 3 days of endocarditis, despite treatment, and are more common in Staphylococcus (especially MRSA) and Enterococcus species. Persistent bacteremia (48-72 h), persistent infection (day 7), and new onset septic shock are related and predict in-hospital mortality. It is, however, persistent infection at day 7 and septic shock that primarily determine the infectious course of endocarditis, and not persistent bacteremia. Valve cultures at surgery become negative in most cases (>85-90%) after 14-21 days of antibiotic therapy, with no calculated benefit for prolonging therapy after 21 days. CONCLUSIONS: Persistent infection at 7 days after appropriate antibiotic therapy is a better key event for prognosis then positive or negative blood cultures at 48-72 h. Therapy prolongation from the day of negative blood cultures is not reasonable. There is no need to survey blood cultures in endocarditis patients after starting therapy.

Evaluation of Quantamatrix dRASTTM system for rapid antimicrobial susceptibility testing of bacterial isolates from positive blood cultures, in comparison with commercial Micronaut broth microdilution system.

Antimicrobial susceptibility testing (AST) from blood culture (BC) may take several days, limiting the eventual impact on antimicrobial stewardship. Hence, rapid AST systems represent a valuable support in shorting the time-to-response. In this work, the Quantamatrix dRASTTM system (dRAST) was evaluated for rapid AST on 100 monomicrobial BCs (50 Gram-negatives and 50 Gram-positives), including several isolates with clinically relevant resistance mechanisms. AST results were provided in 6-hours, on average. Compared to Micronaut (Merlin) system based on broth microdilution, dRAST exhibited an overall categorical agreement of 92.5 %, essential agreement of 89.0 %, and mean bias of 15.9 %. Category overestimation (potentially leading to unnecessary high-dosage treatment or to exclude active agents) and category underestimation (potentially leading to underdosing or using ineffective agents) were observed in 4.3 % and 3.1 % of cases, respectively. Even though several issues were reported, results confirmed the potential contribution of dRAST to shorten the BCs clinical microbiology workflow and management.

Risk factors of bloodstream infection in erythroderma from atopic dermatitis, psoriasis, and drug reactions: a retrospective observational cohort study.

Background: Atopic dermatitis (AD), psoriasis, and drug reactions associated with erythroderma are frequently complicated by infections. However, bloodstream infection (BSI) have received less research attention. Objectives: This study aimed to investigate the clinical characteristics and risk factors associated with BSI in patients with erythroderma. Methods: A retrospective analysis was conducted on 141 erythroderma cases. Eleven cases were identified as having BSI. Clinical records of both BSI and non-BSI groups were reviewed and compared. Results: BSI was diagnosed in 7.80% (11/141) of erythroderma cases, with a breakdown of 7.14% in AD, 2.00% in psoriasis, and 17.14% in drug reactions. Notably, all positive skin cultures (7/7) showed bacterial isolates concordant with blood cultures. Univariate logistic regression analysis revealed several significant associations with BSI, including temperature (≤36.0 or ≥38.5 °C; odds ratio (OR) = 28.06; p < 0.001), chilling (OR = 22.10; p < 0.001), kidney disease (OR = 14.64; p < 0.001), etiology of drug reactions (OR = 4.18; p = 0.03), albumin (ALB) (OR = 0.86; p < 0.01), C-reaction protein (CRP) (OR = 1.01; p = 0.02), interleukin 6 (IL-6) (OR = 1.02; p = 0.02), and procalcitonin (PCT) (OR = 1.07; p = 0.03). Receiver operating characteristic (ROC) curves demonstrated significant associations with ALB (p < 0.001; the area under curve (AUC) = 0.80), PCT (p = 0.009; AUC = 0.74), and CRP (p = 0.02; AUC = 0.71). Conclusions: Increased awareness of BSI risk is essential in erythroderma management. Patients with specific risk factors, such as abnormal body temperature (≤36.0 or ≥38.5 °C), chilling sensations, kidney disease, a history of drug reactions, elevated CRP (≥32 mg/L), elevated PCT (≥1.00 ng/ml), and low albumin (≤31.0 g/L), require close monitoring for BSI development.

Comparison of time-to-detection of Mindray TDR and BacT/ALERT®3D blood culture systems using simulated blood cultures.

PURPOSE: Blood culture (BC) is the standard for diagnosing bloodstream infections. Available blood culture (BC) systems have been developed to shorten the time to detection (TTD) of positive BCs. This study aimed to evaluate the performance of the Mindray TDR automatic BC system by comparing it with the BacT/ALERT®3D system. METHODS: Sixteen reference strains and 14 clinical isolates were used. Serial dilutions were prepared from all bacterial and yeast colonies with a final concentration of 100 CFU/ml and 10 CFU/ml. The prepared solutions were simultaneously inoculated into the bottles of both systems and placed in blood culture devices. RESULTS: Three hundred and fifty-two (176 BacT/ALERT®3D and 176 Mindray TDR-X060) blood culture bottles were evaluated, 336 aerobic and 16 anaerobic. At both 10 CFU/ml and 100 CFU/ml dilution, there was no significant difference between the two systems in terms of mean detection times for all isolates (p = 0.965, p = 0.245). When evaluated according to the type of organism, the detection time of gram-positive bacteria at 10 CFU/ml dilution was significantly shorter in the BacT/ALERT system (p = 0.019), whereas detection time for yeasts was significantly shorter with the Mindray system (p = 0.047). The number of anaerobic bacteria was too small to draw statistical conclusions, but we observed a trend of shorter detection times in the Mindray TDR-X060 system. CONCLUSION: Two systems with similar operating principles showed different concentrations-dependent performances in terms of positivity detection times depending on the type of microorganism. Mindray TDR-X060 system has been found to be safe to use at high concentrations with this at lower concentrations further comparative studies are needed on the newly introduced Mindray system.

Bacteremia caused by Veillonella parvula: Two case reports and a review of the literature.

Veillonella parvula is a non-motile Gram-negative coccus that forms part of the normal microbiota in several body sites and which has been rarely isolated as cause of infections in human population, particularly in bacteremias. Here we give the overview of characteristics of genus Veillonella and the summary of its role in infections, particularly in bacteremia. We additionally report two patients with bacteremia due to V. parvula. Two sets of blood cultures of each patient yielded a pure culture of an anaerobic microorganism identified as V. parvula by MALDI-TOF MS, and confirmed by 16S rRNA gene sequencing. The two patients were male and one of them had risk factors for anaerobic bacteremia. The isolates were susceptible to most antibiotics and the outcome was successful in both patients. Bacteremia due to V. parvula is still rare. MALDI-TOF MS appear to be an excellent tool for the correct identification of these species.

Accelerated microbial identification "directly" from positive blood cultures using MALDI-TOF MS: Local clinical laboratory challenges.

Rapid identification of microbial pathogens "directly" from positive blood cultures (PBCs) is critical for prompt initiation of empirical antibiotic therapy and clinical outcomes. Towards higher microbial identification rates, we modified a published initial serum separator tubes-based MALDI-TOF-MS protocol, for blood culture specimens received at a non-hospital based standalone diagnostic laboratory, Bangalore, India: (a) "Initial" protocol #1: From 28 PBCs, identification= 39% (Gram-negative= 43%: Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa; Gram-positive: 36%: Enterococcus faecalis, Staphylococcus aureus, Staphylococcus haemolyticus); mis-identification= 14%; non-identification= 47%. (b) "Modified" protocol #2: Quality controls (ATCC colonies spiked in negative blood cultures) From 7 analysis, identification= 100% (Escherichia coli, Klebsiella pneumonia, Klebsiella oxytoca, Pseudomonas aeruginosa, Enterococcus faecalis, Staphylococcus aureus); From 7 PBCs, identification= 57%; mis-identification= 14%; non-identification= 29%. Microbial preparations of highest quality and quantity for proteomic analysis and separate spectra matching reference databases for colonies and PBCs are needed for best clinical utility.

Performance of ePlex® blood culture identification panels in clinical isolates and characterization of antimicrobial stewardship opportunities.

We assessed the performance of GenMark's ePlex® Blood Culture Identification (BCID) Panels for overall agreement of organism identification and resistance mechanism detection with standard microbiologic methods. This study included patients with a positive blood culture from May 2020 to January 2021. The primary outcomes were to assess concordance of ePlex® organism identification with standard identification methods and concordance of ePlex® genotypic resistance mechanism detection with standard phenotypic susceptibility testing. Secondary outcomes included panel specific performance and characterization of antimicrobial stewardship opportunities. The overall identification concordance rate in 1276 positive blood cultures was 98.1%. The overall concordance for the presence of resistance markers was 98.2% and concordance for the absence of resistance markers was 100%. A majority of ePlex® results (69.5%) represented opportunities for potential antimicrobial stewardship intervention. High concordance rates between the ePlex® BCID panels and standard identification and susceptibility methods enable utilization of results to guide rapid antimicrobial optimization.

Evaluation of an automated rapid phenotypic antimicrobial susceptibility testing (ASTar, Q-linea AB) applied directly on blood cultures bottles positive for Gram-negative pathogens.

We evaluated the performance of a new rapid phenotypic antimicrobial susceptibility test (ASTar; Q-linea AB) on Gram-negative bacilli, directly from positive blood cultures bottles. MIC values obtained by the routine reference method (Microscan, Beckman Coulter) were compared to the ones provided by the tested method (ASTar). ASTar demonstrated an overall essential agreement of 98% and a category agreement of 96.1%. The overall rate of major errors and very major errors was 2.5% and 3.3%, respectively. ASTar can represent a rapid, simple, and reliable method to speed up information about antimicrobial susceptibility of Gram-negative pathogens from positive blood culture bottles.

A multisite validation of a two hours antibiotic susceptibility flow cytometry assay directly from positive blood cultures.

BACKGROUND: Rapid antimicrobial susceptibility testing (AST) is urgently needed to provide safer treatment to counteract antimicrobial resistance. This is critical in septic patients, because resistance increases empiric therapy uncertainty and the risk of a poor outcome. We validate a novel 2h flow cytometry AST assay directly from positive blood cultures (PBC) by using a room temperature stable FASTgramneg and FASTgrampos kits (FASTinov® Porto, Portugal) in three sites: FASTinov (site-1), Hospital Ramon y Cajal, Madrid, Spain (site-2) and Centro Hospitalar S. João, Porto, Portugal (site-3). A total of 670 PBC were included: 333 spiked (site-1) and 337 clinical PBC (151 site-2 and 186 site-3): 367 gram-negative and 303 gram-positive. Manufacturer instructions were followed for sample preparation, panel inoculation, incubation (1h/37ºC) and flow cytometry analysis using CytoFlex (Site-1 and -2) or DxFlex (site-3) both instruments from Beckman-Coulter, USA. RESULTS: A proprietary software (bioFAST) was used to immediately generate a susceptibility report in less than 2 h. In parallel, samples were processed according to reference AST methods (disk diffusion and/or microdilution) and interpreted with EUCAST and CLSI criteria. Additionally, ten samples were spiked in all sites for inter-laboratory reproducibility. Sensitivity and specificity were >95% for all antimicrobials. Reproducibility was 96.8%/95.0% for FASTgramneg and 95.1%/95.1% for FASTgrampos regarding EUCAST/CLSI criteria, respectively. CONCLUSION: FASTinov® kits consistently provide ultra-rapid AST in 2h with high accuracy and reproducibility on both Gram-negative and Gram-positive bacteria. This technology creates a new paradigm in bacterial infection management and holds the potential to significantly impact septic patient outcomes and antimicrobial stewardship.

Sequential Time to Positivity as a Prognostic Indicator in Staphylococcus aureus Bacteremia.

Background: We aimed to determine the factors associated with sequential blood culture time to positivity (STTP) and validate the previously defined time to positivity (TTP) ratio threshold of 1.5 in predicting adverse disease outcomes and mortality of Staphylococcus aureus bacteremia (SAB). Methods: We conducted an observational study of adult patients with SAB. The TTP ratio was calculated by dividing the TTP of the second blood culture by that of the first. Results: Of 186 patients, 69 (37%) were female, with a mean age of 63.6 years. Median TTP was 12 hours (interquartile range [IQR], 10-15 hours) from the initial and 21 hours (17-29) from sequential blood cultures. Methicillin-resistant S aureus (MRSA)-infected patients had significantly shorter STTPs (P < .001) and lower TTP ratios (P < .001) compared to patients with methicillin-susceptible S aureus (MSSA). A significant correlation between initial and STTP was observed in patients with MRSA (r = 0.42, P = .002) but not in those with MSSA. A higher rate of native valve endocarditis (NVE) significantly correlated with a TTP ratio of ≤1.5 (odds ratio, 2.65 [95% confidence interval, 1.3-5.6]; P = .01). The subgroup having an initial TTP <12 hours combined with a TTP ratio ≤1.5 showed the highest prevalence of NVE. Conclusions: The STTP varies based on methicillin susceptibility of S aureus isolate. This study suggests a potential clinical utility of the STTP to identify patients at a higher risk of NVE. However, prospective studies are required to validate these findings.

Rapid antibiotic susceptibility testing (RAST) of blood cultures in enterobacteria with inducible chromosomal AmpC-type ß-lactamase.

INTRODUCTION: Early and adequate treatment of bloodstream infections decreases patient morbidity and mortality. The objective is to develop a preliminary method for rapid antibiotic susceptibility testing (RAST) in enterobacteria with inducible chromosomal AmpC. METHODS: RAST was performed directly on spiked blood cultures of 49 enterobacteria with inducible chromosomal AmpC. Results were read at 4, 6 and 8h of incubation. Commercial broth microdilution was considered the reference method. Disks of 10 antibiotics were evaluated. RESULTS: The proportion of readable tests at 4h was 85%. All RAST could be read at 6 and 8h. For most antibiotics, the S or R result at 4, 6 and 8h was greater than 80% after tentative breakpoints were established and Area of Technical Uncertainty was defined. CONCLUSIONS: This preliminary method seems to be of practical use, although it should be extended to adjust the breakpoints and differentiate them by species.

Epidemiological patterns of candidaemia: A comprehensive analysis over a decade.

BACKGROUND: The prevalence of fungal bloodstream infections (BSI), especially candidaemia, has been increasing globally during the last decades. Fungal diagnosis is still challenging due to the slow growth of fungal microorganisms and need for special expertise. Fungal polymicrobial infections further complicate the diagnosis and extend the time required. Epidemiological data are vital to generate effective empirical treatment strategies. OBJECTIVES: The overall aim of this project is to describe the epidemiology of monomicrobial candidaemia and polymicrobial BSI, both with mixed fungaemia and with mixed Candida/bacterial BSIs. METHODS: We conducted a single-centre retrospective epidemiological study that encompasses 950,161 blood cultures during the years 2010 to 2020. The epidemiology of monomicrobial and polymicrobial candidaemia episodes were investigated from the electronic records. RESULTS: We found that 1334 candidaemia episodes were identified belonging to 1144 individual patients during 2010 to 2020. Candida albicans was the most prevalent species detected in candidaemia patients, representing 57.7% of these episodes. Nakaseomyces (Candida) glabrata and Candida parapsilosis complex showed an increasing trend compared to previous studies, whereas Candida albicans demonstrated a decrease. 19.8% of these episodes were polymicrobial and 17% presented with mixed Candida/bacterial BSIs while 2.8% were mixed fungaemia. C. albicans and N. glabrata were the most common combination (51.4%) in mixed fungaemia episodes. Enterococcus and Lactobacillus spp. were the most common bacteria isolated in mixed Candida/bacterial BSIs. CONCLUSIONS: Polymicrobial growth with candidaemia is common, mostly being mixed Candida/bacterial BSIs. C. albicans was detected in more than half of all the candidaemia patients however showed a decreasing trend in time, whereas an increase is noteworthy in C. parapsilosis complex and N. glabrata.

Rise in the Pathogenic Status of Coagulase-Negative Staphylococci Causing Bloodstream Infection.

BACKGROUND: Coagulase-negative staphylococci (CoNS) are one of the frequently isolated bacteria from blood cultures. Since they are part of the normal skin flora, they were previously considered contaminants. But now, they can be considered as established pathogens causing bloodstream infection (BSI). This study aims to estimate the prevalence of CoNS in BSI cases. METHODS: This study was conducted at the Microbiology Department, All India Institute of Medical Sciences (AIIMS), Raipur, India, for eight months (January 2022 to August 2022). Data were collected retrospectively from medical and laboratory records. Paired blood cultures from 5085 clinically suspected sepsis cases were subjected to aerobic culture for five days in the BacT ALERT 3D system. Pathogenicity was established after recovery of CoNS from paired blood cultures of symptomatic patients. RESULTS: CoNS were isolated from 2.35% of patients, the most common species being Staphylococcus haemolyticus (51.67%). About 90% of isolates were methicillin-resistant. All the isolates were susceptible to linezolid, teicoplanin, and vancomycin, except one isolate of S. haemolyticus which was intermediate to vancomycin. Minimum inhibitory concentration (MIC) 50 and MIC 90 for vancomycin were 1 ug/ml and 2 ug/ml, respectively.  Conclusion: Paired blood cultures are necessary to determine the pathogenicity of CoNS in BSI cases. A high prevalence of methicillin resistance, accompanied by high resistance rates to other non-beta lactam antibiotics, warrants the strict implementation of antimicrobial stewardship practices.

Association of persistent positive blood cultures and infective endocarditis: A cohort study among patients with suspected infective endocarditis.

OBJECTIVES: To ascertain whether infective endocarditis (IE) was associated with persistent bacteraemia/candidaemia among patients with suspected IE. METHODS: This study included bacteraemic/candidaemic adult patients with echocardiography and follow-up blood cultures. Persistent bacteraemia/candidaemia was defined as continued positive blood cultures with the same microorganism for 48 h or more after antibiotic treatment initiation. Each case was classified for IE by the Endocarditis Team. RESULTS: Among 1962 episodes of suspected IE, IE (605; 31%) was the most prevalent infection type. Persistent bacteraemia/candidaemia was observed in 426 (22%) episodes. Persistent bacteraemia was more common among episodes with Staphylococcus aureus bacteraemia compared to episodes with positive blood cultures for other pathogens (32%, 298/933 vs 12%, 128/1029; P < 0.001). Multivariable analysis demonstrated that cardiac predisposing factors (aOR 1.84, 95% CI 1.31-2.60), community or non-nosocomial healthcare-associated (2.85, 2.10-3.88), bacteraemia by high-risk bacteria, such as S. aureus, streptococci, enterococci or HACEK (1.84, 1.31-2.60), two or more positive sets of index blood cultures (6.99, 4.60-10.63), persistent bacteraemia/candidaemia for 48 h from antimicrobial treatment initiation (1.43, 1.05-1.93), embolic events within 48h from antimicrobial treatment initiation (12.81, 9.43-17.41), and immunological phenomena (3.87, 1.09-1.78) were associated with infective endocarditis. CONCLUSIONS: IE was associated with persistent bacteraemia/candidaemia, along with other commonly associated factors.

Pediatric blood cultures-turning up the volume: a before and after intervention study.

The major determinant of blood culture (BC) diagnostic performance is blood volume, and pediatric sample volumes are frequently low. We aimed to assess BC volumes in our institution, design an intervention to increase volumes, and assess its impact. All pediatric BCs submitted over a 7-month period to the microbiology laboratory in a university hospital (including emergency department, pediatric ward, and neonatal unit) were included. A pre-intervention period assessed current practice. A multi-faceted intervention (education, guideline introduction, active feedback strategies) was collaboratively designed by all stakeholders. Impact was assessed in a post-intervention period. The main outcome measures included the percentage of samples adequately filled using three measures of sample adequacy (1) manufacturer-recommended minimum validated volume-> 0.5 ml, (2) manufacturer-recommended optimal minimum volume-> 1.0 ml, (3) newly introduced age-specific recommendations. Three hundred ninety-eight pre-intervention and 388 post-intervention samples were included. Initial volumes were low but increased significantly post-intervention (median 0.77 ml vs. 1.52 ml), with multivariable regression analysis estimating volumes increased 89% post-intervention. There were significant increases in all measures of volume adequacy, including an increase in age-appropriate filling (20.4-53.1%), with less improvement in those aged > 3 years. Overall, 68.4% of pathogens were from adequately filled cultures, while 76% of contaminants were from inadequately filled cultures. A pathogen was detected in a higher proportion of adequately filled than inadequately filled cultures (9.4% vs. 2.2%, p < 0.001).  Conclusion: Blood volume impacts BC sensitivity, with lower volumes yielding fewer pathogens and more contaminants. Focused intervention can significantly improve volumes to improve diagnostic performance. What is Known: • Blood volume is the major determinant of blood culture positivity, and yet pediatric blood culture volumes are frequently low, resulting in missed pathogens and increased contamination. What is New: • Adequately filled (for age) blood cultures have a pathogen detection rate three times higher than inadequately filled blood cultures. • This interventional study shows that collaboratively designed multi-modal interventions including focus on accurate volume measurement can lead to significant increases in blood volumes and improve blood culture diagnostic performance.

[Infections and fever]. / Infektion und Fieber.

Fever can be due to infectious or noninfectious causes and results from the body's natural response to exogenous or endogenous pyrogens. Laboratory tests including complete blood count, differential blood count, C­reactive protein, erythrocyte sedimentation rate and procalcitonin do not have sufficient sensitivity and specificity to definitively detect or rule out an infectious (bacterial, viral, parasitic) cause of fever. Blood cultures should be carried out when bacteremic or septic illnesses are suspected. Fever is not always present in infections and can be absent, especially in older and immunocompromised patients. If fever is suspected, core temperatures should be taken, e.g., rectally, orally or invasively. Depending on the clinical situation, infectious causes must be excluded as the most likely cause of an acutely occurring fever. The investigation of long-standing fever (fever of unknown origin, FUO) can be complex and some infectious diseases should first be ruled out, whereby a syndromic classification often helps to clarify the cause of the fever.