Relation between the Dantu blood group variant and bacteraemia in Kenyan children: a population-based case control study.

BACKGROUND: The Dantu blood group variant protects against P. falciparum infections but its wider consequences have not been previously explored. Here, we investigate the impact of Dantu on susceptibility to bacteraemia. METHODS: We conducted a case-control study in children presenting with community-acquired bacteraemia to Kilifi County Hospital in Kenya between 1998 and 2010. We used logistic regression to test for associations between the Dantu marker SNP rs186873296 A>G and both all-cause and pathogen-specific bacteraemia under an additive model. We used date of admission as a proxy measure of malaria transmission intensity, given known differences in malaria prevalence over the course of the study. RESULTS: Dantu was associated with protection from all-cause bacteraemia (OR=0.81, p=0.014), the association being greatest in homozygotes (OR=0.30, p=0.013). This protection was shared across the major bacterial pathogens but, notably, was only significant during the era of high malaria-transmission pre-2003 (OR=0.79, p=0.023). CONCLUSIONS: Consistent with previous studies showing the indirect impact on bacteraemia risk of other malaria-associated red cell variants, our study also shows that Dantu is protective against bacteraemia via its effect on malaria risk. Dantu does not appear to be under balancing selection through an increased risk of bacterial infections.

Distinct Clinical Endpoints of Staphylococcus aureus Bacteraemia Complicate Assessment of Outcome.

BACKGROUND: We aimed to test the hypothesis that development of metastatic infection represents a distinct clinical endpoint from death due to Staphylococcus aureus bacteremia (SAB). METHODS: We conducted a retrospective observational study of adults with SAB between 20 December 2019 and 23 August st2022 (n = 464). Simple logistic regression, odds ratios, and z-scores were used to compare host, clinical, and microbiologic features. RESULTS: Co-occurrence of attributable mortality and metastatic infection was infrequent. Charlson Comorbidity Index and age were strongly associated with attributable mortality, but not metastatic infection. We compared patients with fatal SAB (without clinically-apparent metastatic complications, 14.4% of cohort), metastatic SAB (without attributable mortality, 22.2%), neither complication (56.7%), and overlapping fatal/metastatic SAB (6.7%). Compared to SAB without complications, fatal SAB was specifically associated with older age and multi-morbidity. Metastatic SAB was specifically associated with community acquisition, persistent fever, persistent bacteremia, and recurrence. Endocarditis was over-represented in the fatal/metastatic SAB overlap group, which shared patient characteristics with fatal SAB. In contrast to other (predominantly musculoskeletal) metastatic complications, endocarditis was associated with increased mortality, with death occurring in older multi-morbid patients later after SAB onset. CONCLUSIONS: Patients with SAB experience distinct clinical endpoints: (i) early death, associated with multi-morbidity and age; (ii) metastatic (predominantly musculoskeletal) SAB; (iii) endocarditis, associated with late death occurring in older people with multi-morbidity, and (iv) bacteraemia without complications. These distinctions could be important for selecting appropriate outcomes in clinical trials: different interventions might be required to reduce mortality versus improve clinical response in patients with metastatic SAB.

Bacteriuria in patients with stented ureters: predictors of infection in patients presenting to the hospital and when not to treat.

PURPOSE: Patients with ureteric stents have symptoms that overlap with infection symptoms. Thus, clinicians unnecessarily give antibiotics to stented patients with bacteriuria despite guidelines. In stented patients, little is known about risk factors for developing bacteriuria or urosepsis. The objectives were to identify the frequency and risk factors for developing bacteriuria and urosepsis in patients with stents. METHODS: In this retrospective cohort study, we reviewed patients with ureteric stents placed or exchanged over 1 year. We examined associations between bacteriuria or urosepsis and host risk factors. Univariable and multivariable logistic analyses were performed. RESULTS: Of 286 patients (mean age: 57.2 years), 167 (58.4%) were male. The main stent indications were stone, stricture, cancer and extrinsic compression. The median stented period was 61 days. The frequency of bacteriuria was 59/286 (21%). ASA status 3 and 4 had 5 times the odds of having bacteriuria relative to ASA status 1. Stent duration > 2 months had 5.5 times the odds relative to ≤ 2 months. Urosepsis was infrequent, 13/286 (4.5%). Five patients had bacteraemia. A stent duration over 2 months had nearly 6 times the odds of urosepsis. CONCLUSION: ASA status higher than 2 and stent time greater than 2 months raise the odds of developing bacteriuria. A stent duration longer than 2 months was the only predictor of urosepsis. Though 21% of patients had bacteriuria, 4.5% had urosepsis. Hence, bacteriuria without sepsis should not be treated with antibiotics, thus aiding antimicrobial stewardship.

Bacteraemia caused by non-faecalis and non-faecium Enterococcus species-a retrospective study of incidence, focus of infection, and prognosis.

BACKGROUND/AIM: Enterococcus faecalis and Enterococcus faecium cause human infections including bacteraemia and infective endocarditis (IE). Only few studies describing non-faecalis and non-faecium Enterococcus (NFE) infections have been conducted. We aimed to describe the incidence, prognosis, and focus of infection of bacteraemia with NFE. METHODS: This retrospective population-based study included all episodes of patients having a blood culture with growth of NFE between 2012 and 2019 in Region Skåne, Sweden. Information was collected from medical records. Episodes of bacteraemia caused by NFE were compared to episodes of bacteraemia caused by E. faecalis and E. faecium. RESULTS: During the study period, 136 episodes with NFE bacteraemia were identified corresponding to an incidence of NFE bacteraemia of 16 cases per 1,000,000 person-years among adults. Enterococcus casseliflavus (n=45), Enterococcus gallinarum (n=34), and Enterococcus avium (n=29) were the most common species. The most common foci of infection were biliary tract infections (n=17) followed by gastrointestinal infections (n=7). Urinary tract infections were not commonly caused by NFE (n=1), and no episodes of IE were caused by NFE. Polymicrobial bacteraemia was more common with NFE (73%) than with E. faecalis (35%) and E. faecium (42%). Community acquired infections were more common in bacteraemia with NFE compared to E. faecium. 30- and 90-day survival rates were 76% and 68%, respectively, and recurrent NFE bacteraemia was seen after 3% of the episodes. CONCLUSION: Bacteraemia caused by NFE is rare and is often polymicrobial. Biliary tract focus is common in NFE bacteraemia whereas IE and urinary tract focus are uncommon.

Validation of a new risk stratification system-based management for methicillin-resistant Staphylococcus aureus bacteraemia: analysis of a multicentre prospective study.

PURPOSE: Distinguishing between complicated and uncomplicated Staphylococcus aureus bacteraemia (SAB) is therapeutically essential. However, this distinction has limitations in reflecting the heterogeneity of SAB and encouraging targeted diagnostics. Recently, a new risk stratification system for SAB metastatic infection, involving stepwise approaches to diagnosis and treatment, has been suggested. We assessed its applicability in methicillin-resistant SAB (MRSAB) patients. METHODS: We retrospectively analysed data of a 3-year multicentre, prospective cohort of hospitalised patients with MRSAB. We classified the patients into three risk groups: low, indeterminate, and high, based on the new system and compared between-group management and outcomes. RESULTS: Of 380 patients with MRSAB, 6.3% were classified as low-, 7.6% as indeterminate-, and 86.1% as high-risk for metastatic infection. No metastatic infection occurred in the low-, 6.9% in the indeterminate-, and 19.6% in the high-risk groups (P < 0.001). After an in-depth diagnostic work-up, patients were finally diagnosed as 'without metastatic infection (6.3%)', 'with metastatic infection (17.4%)', and 'uncertain for metastatic infection (76.3%)'. 30-day mortality increased as the severity of diagnosis shifted from 'without metastatic infection' to 'uncertain for metastatic infection' and 'with metastatic infection' (P = 0.09). In multivariable analysis, independent factors associated with metastatic complications were suspicion of endocarditis in transthoracic echocardiography, clinical signs of metastatic infection, Pitt bacteraemia score ≥ 4, and persistent bacteraemia. CONCLUSIONS: The new risk stratification system shows promise in predicting metastatic complications and guiding work-up and management of MRSAB. However, reducing the number of cases labelled as 'high-risk' and 'uncertain for metastatic infection' remains an area for improvement.

Experience with dalbavancin use in various gram-positive infections within Aberdeen Royal Infirmary OPAT service.

PURPOSE: Dalbavancin, approved in 2014 for Gram-positive acute bacterial skin and skin structure infections (ABSSSI), has pharmacokinetics enabling treatment with one or two doses. Dalbavancin might be useful in outpatient parenteral antibiotic therapy (OPAT) of deep-seated infections, otherwise requiring inpatient admission. We documented our experience with pragmatic dalbavancin use to assess its effectiveness for varied indications, on- and off-label, as primary or sequential consolidation therapy. METHODS: Patients prescribed dalbavancin between 1 December 2021 and 1 October 2022 were screened for demographics of age, sex, Charlson comorbidity index (CCI), allergies, pathogens, doses of dalbavancin, other antibiotics administered and surgery. Where available, infection markers were recorded. The primary outcome was a cure at the end of treatment. Secondary outcomes included any adverse events and for those with treatment failures, response to salvage antibiotics. RESULTS: Sixty-seven per cent of patients were cured. Cure rates by indication were 93% for ABSSSI, 100% for bacteraemia, 90% for acute osteomyelitis, 0% for chronic osteomyelitis, 75% for native joint septic arthritis and 33% for prosthetic joint infection. Most bone and joint infections that were not cured did not have source control, and the goal of treatment was suppressive. Successful suppression rates were greater at 48% for chronic osteomyelitis and 66% for prosthetic joint infections. Adverse events occurred in 14 of 102 patients. CONCLUSION: This report adds to clinical experience with dalbavancin for off-label indications whilst further validating its role in ABSSSI. Dalbavancin as primary therapy in deep-seated infections merits investigation in formal clinical trials.

Assessment of a novel BLOOMY score for predicting mortality in hospitalised adults with bloodstream infection.

PURPOSE: A German multicentre study BLOOMY was the first to use machine learning approach to develop mortality prediction scores for bloodstream infection (BSI) patients, but the scores have not been assessed in other cohorts. Our aim was to assess how the BLOOMY 14-day and 6-month scores estimate mortality in our cohort of 497 cases with BSI. METHODS: Clinical data, laboratory data, and patient outcome were gathered retrospectively from patient records. The scores were calculated as presented in the BLOOMY study with the exception in the day of the evaluation. RESULTS: In our cohort, BLOOMY 14-day score estimated death by day 14 with an area under curve (AUC) of 0.87 (95% Confidence Interval 0.80-0.94). Using ≥ 6 points as a cutoff, sensitivity was 68.8%, specificity 88.1%, positive predictive value (PPV) 39.3%, and negative predictive value (NPV) 96.2%. These results were similar in the original BLOOMY cohort and outweighed both quick Sepsis-Related Organ Failure Assessment (AUC 0.76) and Pitt Bacteraemia Score (AUC 0.79) in our cohort. BLOOMY 6-month score to estimate 6-month mortality had an AUC of 0.79 (0.73-0.85). Using ≥ 6 points as a cutoff, sensitivity was 98.3%, specificity 10.7%, PPV 25.7%, and NPV 95.2%. AUCs of 6-month score to estimate 1-year and 5-year mortality were 0.80 (0.74-0.85) and 0.77 (0.73-0.82), respectively. CONCLUSION: The BLOOMY 14-day and 6-month scores performed well in the estimations of mortality in our cohort and exceeded some established scores, but their adoption in clinical work remains to be seen.

Flucloxacillin and cefazolin for treatment of Staphylococcus aureus bloodstream infection.

PURPOSE: Antistaphylococcal penicillins and cefazolin have been used as first line therapy in Methicillin-susceptible Staphylococcus aureus bloodstream infection. While efficacy of both regimens seems to be similar, the compounds may differ with regard to tolerability. This study aims to describe the clinical use of cefazolin and flucloxacillin, focussing on discontinuation or change of anti-infective agent due to adverse events. METHODS: This observational prospective study was conducted at two German tertiary care centres with an internal recommendation of flucloxacillin for MSSA-BSI in one, and of cefazolin in the other centre. Adverse events were registered weekly under treatment and at a 90-day follow-up. Descriptive analysis was complemented by a propensity score analysis comparing adverse events (stratified rank-based test applied to the sum of Common Terminology Criteria for adverse events ratings per patient). RESULTS: Of 71 patients included, therapy was initiated with flucloxacillin in 56 (79%), and with cefazolin in 15 (21%). The propensity score analysis indicates a statistically significant difference concerning the severity of adverse events between the treatment groups in favour of cefazolin (p = 0.019). Adverse events led to discontinuation of flucloxacillin in 7 individuals (13% of all patients receiving flucloxacillin). Clinical outcome was not different among treatment groups. CONCLUSION: Using cefazolin rather than flucloxacillin as a first line agent for treatment of MSSA-BSI is supported by these clinical data.

A systematic review and meta-analysis of ambient temperature and precipitation with infections from five food-borne bacterial pathogens.

Studies on climate variables and food pathogens are either pathogen- or region-specific, necessitating a consolidated view on the subject. This study aims to systematically review all studies on the association of ambient temperature and precipitation on the incidence of gastroenteritis and bacteraemia from Salmonella, Shigella, Campylobacter, Vibrio, and Listeria species. PubMed, Ovid MEDLINE, Scopus, and Web of Science databases were searched up to 9 March 2023. We screened 3,204 articles for eligibility and included 83 studies in the review and three in the meta-analysis. Except for one study on Campylobacter, all showed a positive association between temperature and Salmonella, Shigella, Vibrio sp., and Campylobacter gastroenteritis. Similarly, most of the included studies showed that precipitation was positively associated with these conditions. These positive associations were found regardless of the effect measure chosen. The pooled incidence rate ratio (IRR) for the three studies that included bacteraemia from Campylobacter and Salmonella sp. was 1.05 (95 per cent confidence interval (95% CI): 1.03, 1.06) for extreme temperature and 1.09 (95% CI: 0.99, 1.19) for extreme precipitation. If current climate trends continue, our findings suggest these pathogens would increase patient morbidity, the need for hospitalization, and prolonged antibiotic courses.

Retrospective database analysis for clinical diagnoses commonly associated with pneumococcal diseases in the Malaysian healthcare system over a 3-year period (2013-2015).

BACKGROUND: Pneumococcal disease caused by Streptococcus pneumoniae is an important cause of morbidity and mortality across all ages, particularly in younger children and older adults. Here, we describe pneumococcal disease hospitalizations at Ministry of Health (MoH) facilities in Malaysia between 2013 and 2015. METHODS: This was a retrospective databases analysis. Tabular data from the Malaysian Health Data Warehouse (MyHDW) were used to identify microbiologically confirmed, pneumococcal disease hospitalizations and deaths during hospitalization, using hospital-assigned ICD-10 codes (i.e., classified as meningitis, pneumonia, or non-meningitis non-pneumonia). Case counts, mortality counts, and case fatality rates were reported by patient age group and by Malaysian geographic region. RESULTS: A total of 683 pneumococcal disease hospitalizations were identified from the analysis: 53 pneumococcal meningitis hospitalizations (5 deaths and 48 discharges), 413 pneumococcal pneumonia hospitalizations (24 deaths and 389 discharges), and 205 non-meningitis non-pneumonia pneumococcal disease hospitalizations (58 deaths and 147 discharges). Most hospitalizations occurred in children aged < 2 years. Crude mortality was highest among children aged < 2 years (for all three disease categories), among adults aged ≥ 65 years (for pneumococcal pneumonia), or among adults aged 65-85 years (for non-meningitis non-pneumonia pneumococcal disease). The case fatality rate, all ages included, was 5.8% for pneumococcal pneumonia, 9.1% for pneumococcal meningitis, and 28.3% for non-meningitis non-pneumonia pneumococcal disease. CONCLUSIONS: Our study is the first to document pneumococcal disease hospitalizations and deaths during hospitalization in Malaysia. Although this database analysis likely underestimated case counts, and the true disease burden could be even greater, the study demonstrates a substantial burden of pneumococcal disease. Public health measures, including vaccination, would significantly contribute to the prevention of hospitalizations and deaths associated with pneumococcal disease in Malaysia.

Influence of initial misdiagnosis on mortality in patients with bacteraemia: propensity score matching and propensity score weighting analyses.

BACKGROUND: The diagnostic process is a key element of medicine but it is complex and prone to errors. Infectious diseases are one of the three categories of diseases in which diagnostic errors can be most harmful to patients. In this study we aimed to estimate the effect of initial misdiagnosis of the source of infection in patients with bacteraemia on 14 day mortality using propensity score methods to adjust for confounding. METHODS: Data from a previously described longitudinal cohort of patients diagnosed with monobacterial bloodstream infection (BSI) at the Leiden University Medical Centre (LUMC) between 2013 and 2015 were used. Propensity score matching and inversed probability of treatment weighting (IPTW) were applied to correct for confounding. The average treatment effect on the treated (ATT), which in this study was the average effect of initial misdiagnosis on the misdiagnosed (AEMM), was estimated. Methodological issues that were encountered when applying propensity score methods were addressed by performing additional sensitivity analyses. Sensitivity analyses consisted of varying caliper in propensity score matching and using different truncated weights in inversed probability of treatment weighting. RESULTS: Data of 887 patients were included in the study. Propensity scores ranged between 0.015 and 0.999 and 80 patients (9.9%) had a propensity score > 0.95. In the matched analyses, 35 of the 171 misdiagnosed patients died within 14 days (20.5%), versus 10 of the 171 correctly diagnosed patients (5.8%), yielding a difference of 14.6% (7.6%; 21.6%). In the total group of patients, the observed percentage of patients with an incorrect initial diagnosis that died within 14 days was 19.8% while propensity score reweighting estimated that their probability of dying would have been 6.5%, if they had been correctly diagnosed (difference 13.3% (95% CI 6.9%;19.6%)). After adjustment for all variables that showed disbalance in the propensity score a difference of 13.7% (7.4%; 19.9%) was estimated. Sensitivity analyses yielded similar results. However, performing weighted analyses without truncation yielded unstable results. CONCLUSION: Thus, we observed a substantial increase of 14 day mortality in initially misdiagnosed patients. Furthermore, several patients received propensity scores extremely close to one and were almost sure to be initially misdiagnosed.

Clinical outcome of combination of vancomycin and ceftaroline versus vancomycin monotherapy for treatment of methicillin resistant Staphylococcus aureus bloodstream infection.

BACKGROUND: The role of combination therapies for serious methicillin-resistant Staphylococcus aureus (MRSA) infections is widely debated. METHODS: This retrospective cohort study included adults with MRSA bacteraemia treated between January 1, 2013, to December 31, 2022. Patients receiving combination therapy with vancomycin and ceftaroline were matched in a 2:1 ratio with those on vancomycin monotherapy based on bacteraemia source and illness severity. The primary outcome was frequency of bacteraemia recurrence. Secondary outcomes were all cause 30/90-day mortality, recurrence or mortality at 30/90 days and in hospital length of stay. RESULTS: Of 57 patients included, 37 (65%) were in the combination group. The overall intensive care unit admission rate was 63.2% (36/57) and the Pitt Bacteraemia Score was 1 [0-4] at the time of diagnosis. The most common source of infection was endovascular/endocarditis (n = 36, 63.2%). Demographic and clinical characteristics were similar between the monotherapy and combination group of patients, except for higher body mass index (32.5 [25.5-36.4] vs. 24.4 [20.9-29], p = 0.004) and a greater immunosuppression prevalence (3 (15%) vs. 0 (0%), p = 0.039) in monotherapy group. There was no significant difference in bacteraemia recurrence (3 (15%) vs. 4 (10.8%), p = 0.7) or all-cause 30-day mortality (3 (15%) vs. 4 (10.8%), p = 0.7) between the two groups. CONCLUSION: The results of this study are limited by a retrospective observational design; however, combination of vancomycin and ceftaroline for MRSA bacteraemia was not associated with lower bacteraemia recurrence or mortality compared to vancomycin monotherapy.

Rare case of septic shock combined with meningitis caused by Pasteurella multocida without a history of cat and dog bites.

BACKGROUND: Pasteurella multocida is a zoonotic pathogen that mainly causes local skin and soft tissue infections in the human body through cat and dog bites. It rarely causes bacteraemia (or sepsis) and meningitis. We reported a case of septic shock and meningitis caused by P. multocida in a patient without a history of cat and dog bites. CASE PRESENTATION: An 84-year-old male patient was urgently sent to the emergency department after he was found with unclear consciousness for 8 h, accompanied by limb tremors and urinary incontinence. In the subsequent examination, P. multocida was detected in the blood culture and wound secretion samples of the patient. However, it was not detected in the cerebrospinal fluid culture, but its DNA sequence was detected. Therefore, the patient was clearly diagnosed with septic shock and meningitis caused by P. multocida. The patient had no history of cat or dog contact or bite. The patient was subsequently treated with a combination of penicillin G, doxycycline, and ceftriaxone, and he was discharged after 35 days of hospitalisation. CONCLUSION: This report presented a rare case of septic shock and meningitis caused by P. multocida, which was not related to a cat or dog bite. Clinical doctors should consider P. multocida as a possible cause of sepsis or meningitis and should be aware of its potential seriousness even in the absence of animal bites.

Ruthenibacterium lactatiformans isolated from a human blood culture: a first report.

BACKGROUND: Ruthenibacterium lactatiformans, a Gram-stain-negative, rod-shaped, obligate anaerobic bacterium of the Oscillospiraceae family, has not been previously reported in human infections. This study reports the first case of bacteraemia and potential vertebral osteomyelitis caused by Ruthenibacterium lactatiformans. CASE PRESENTATION: An 82-year-old man with a history of diabetes, chronic renal failure, and prior spinal surgery for spondylolisthesis and spinal stenosis presented with fever and lower back pain. Magnetic resonance imaging revealed multiple vertebral osteomyelitis lesions. Initial blood cultures identified methicillin-resistant Staphylococcus aureus (MRSA), which prompted vancomycin treatment. However, repeated blood cultures not only confirmed persistent MRSA, but also detected Gram-negative bacilli (GNB). Despite surgical removal of the spinal hardware and antimicrobial therapy, the patient's osteomyelitis worsened, necessitating transfer for further management. Subsequent analysis using 16S rRNA gene sequencing identified the GNB as Ruthenibacterium lactatiformans. CONCLUSIONS: This is the first documented instance of human infection with Ruthenibacterium lactatiformans, signifying its pathogenic potential in vertebral osteomyelitis. The involvement of anaerobic bacteria and the possibility of polymicrobial infections complicate the diagnosis and treatment of vertebral osteomyelitis. This report underscores the need for caution when identifying the causative organism and selecting an appropriate treatment.

Predicting community acquired bloodstream infection in infants using full blood count parameters and C-reactive protein; a machine learning study.

Early recognition of bloodstream infection (BSI) in infants can be difficult, as symptoms may be non-specific, and culture can take up to 48 h. As a result, many infants receive unneeded antibiotic treatment while awaiting the culture results. In this study, we aimed to develop a model that can reliably identify infants who do not have positive blood cultures (and, by extension, BSI) based on the full blood count (FBC) and C-reactive protein (CRP) values. Several models (i.e. multivariable logistic regression, linear discriminant analysis, K nearest neighbors, support vector machine, random forest model and decision tree) were trained using FBC and CRP values of 2693 infants aged 7 to 60 days with suspected BSI between 2005 and 2022 in a tertiary paediatric hospital in Dublin, Ireland. All models tested showed similar sensitivities (range 47% - 62%) and specificities (range 85%-95%). A trained decision tree and random forest model were applied to the full dataset and to a dataset containing infants with suspected BSI in 2023 and showed good segregation of a low-risk and high-risk group. Negative predictive values for these two models were high for the full dataset (> 99%) and for the 2023 dataset (> 97%), while positive predictive values were low in both dataset (4%-20%).   Conclusion: We identified several models that can predict positive blood cultures in infants with suspected BSI aged 7 to 60 days. Application of these models could prevent administration of antimicrobial treatment and burdensome diagnostics in infants who do not need them. What is Known: • Bloodstream infection (BSI) in infants cause non-specific symptoms and may be difficult to diagnose. • Results of blood cultures can take up to 48 hours. What is New: • Machine learning models can contribute to clinical decision making on BSI in infants while blood culture results are not yet known.

Vibrio species bloodstream infections in Queensland, Australia.

BACKGROUND: Vibrio species bloodstream infections have been associated with significant mortality and morbidity. Limited information is available regarding the epidemiology of bloodstream infections because of Vibrio species in the Australian context. AIMS: The objective of this study was to define the incidence and risk factors for developing Vibrio species bloodstream infections and compare differences between different species. METHODS: All patients with Vibrio spp. isolated from positive blood cultures between 1 January 2000 and 31 December 2019 were identified by the state-wide Pathology Queensland laboratory. Demographics, clinical foci of infections and comorbid conditions were collected in addition to antimicrobial susceptibility results. RESULTS: About 100 cases were identified between 2000 and 2019 with an incidence of 1.2 cases/1 million person-years. Seasonal and geographical variation occurred with the highest incidence in the summer months and in the tropical north. Increasing age, male sex and multiple comorbidities were identified as risk factors. Vibrio vulnificus was isolated most frequently and associated with the most severe disease. Overall case fatality was 19%. CONCLUSIONS: There is potential for increasing cases of Vibrio species infections globally with ageing populations and climate change. Ongoing clinical awareness is required to ensure optimal patient outcomes.

Predictive value of urine microscopy and urine culture in bacteraemic adults without localising urinary features.

BACKGROUND: Urine microscopy (UM) and urine culture (UC) are used in bacteraemic patients to identify a urinary focus of infection. However, their positive and negative predictive values (PPV and NPV) in patients without localising urinary features are uncertain. AIMS: We aimed to determine the predictive value of UM/UC for diagnosing bacteraemic urinary tract infection (bUTI) in bacteraemic patients without localising urinary features. METHODS: A retrospective study of bacteraemic adults was conducted. PPV and NPV of UM/UC for bacteraemic urinary tract infection (bUTI) was determined in two subgroups of patients without localising urinary features: those with an unclear focus of infection, and those with a suspected non-urinary focus of infection. In those with an unclear focus, univariate analysis for risk factors associated with bUTI was performed. RESULTS: A total of 871 patients were included. Localising urinary features were absent in 110 of 342 patients (32.2%) with bUTI. In patients with an unclear focus, UM had a PPV of 51.5% and an NPV of 96% for bUTI, and UC had a PPV of 75% and an NPV of 88.6%. In patients with a suspected non-urinary focus, UM had a PPV of 5.2% and an NPV of 100%, and UC had a PPV of 25% and an NPV of 99.5%. While some risk factors for bUTI in patients with an unclear focus were identified, 22 of 98 patients (22.4%) had bUTI despite no risk factors. CONCLUSIONS: bUTI without localising urinary features is common. In bacteraemia of unclear focus, UM/UC has a high NPV for excluding bUTI, although PPV is limited and non-urinary foci require consideration despite a positive result. UM/UC is low yield in those with a suspected non-urinary focus of infection.

Avoiding misclassification of acute kidney injury: Timing is everything.

Accurate detection of acute kidney injury (AKI) in clinical trials is important. Using a 'baseline' creatinine from trial enrolment may not be ideal for understanding a participant's true baseline kidney function. We aimed to determine if a 'pre-trial baseline creatinine' resulted in comparable creatinine concentrations to a 'trial baseline creatinine', and how the timing of baseline creatinine affected the incidence of AKI in the Combination Antibiotic therapy for MEthicillin Resistant Staphylococcus aureus (CAMERA2) randomised trial. Study sites retrospectively collected a pre-trial baseline creatinine from up to 1 year before CAMERA2 trial enrolment ideally when the patient was medically stable. Baseline creatinine from CAMERA2 (the 'trial baseline creatinine'), was the highest creatinine measurement in the 24 h preceding trial randomisation. We used Wilcoxon sign rank test to compare pre-trial and trial baseline creatinine concentrations. We included 217 patients. The median pre-trial baseline creatinine was significantly lower than the median trial baseline creatinine (82 µmol/L [IQR 65-104 µmol/L] versus 86 µmol/L [IQR 66-152 µmol/L] p = <0.001). Using pre-trial baseline creatinine, 48 of 217 patients (22%) met criteria for an AKI at CAMERA2 enrolment and only 5 of these patients met criteria for an AKI using the CAMERA2 study protocol (using baseline creatinine from trial entry). Using a baseline creatinine from the time of trial enrolment failed to detect many patients with AKI. Trial protocols should consider the optimal timing of baseline creatinine and the limitations of using a baseline creatinine during an acute illness.

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

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

Early oral antibiotic switch in Staphylococcus aureus bacteraemia: The Staphylococcus aureus Network Adaptive Platform (SNAP) Trial Early Oral Switch Protocol.

BACKGROUND: Staphylococcus aureus bloodstream infection (bacteraemia) is traditionally treated with at least two weeks of IV antibiotics in adults, 3-7 days in children, and often longer for those with complicated disease. The current practice of treating S. aureus bacteraemia (SAB) with prolonged IV antibiotics (rather than oral antibiotics) is based on historical observational research and expert opinion. Prolonged IV antibiotic therapy has significant disadvantages for patients and healthcare systems, and there is growing interest in whether a switch to oral antibiotics following an initial period of IV therapy is a safe alternative for clinically stable patients. PROTOCOL: The early oral switch (EOS) domain of the S. aureus Network Adaptive Platform (SNAP) trial will assess early switch to oral antibiotics compared with continued IV treatment in clinically stable patients with SAB. The primary endpoint is 90-day all-cause mortality. Hospitalised SAB patients are assessed at platform day 7 +/- 2 (uncomplicated SAB) and day 14 +/-2 (complicated SAB) to determine their eligibility for randomisation to EOS (intervention) or continued IV treatment (current standard of care). DISCUSSION: Recruitment is occurring to the EOS domain of the SNAP trial. As of August 2023, 21% of all SNAP participants had been randomised to the EOS domain, a total of 264 participants across 77 centres, with an aim to recruit at least 1000 participants. We describe challenges and facilitators to enrolment in this domain to aid those planning similar trials.