Colorectal cancer and association with anaerobic bacteraemia: A Danish nationwide population-based cohort study.

OBJECTIVES: We aimed to identify specific anaerobic bacteria causing bacteraemia and a subsequent diagnosis of colorectal cancer. METHODS: A nationwide population-based cohort study, which included all episodes of defined specific anaerobic bacteraemia from 2010 (5,534,738 inhabitants) through 2020 (5,822,763 inhabitants) and all cases of colorectal cancer diagnosed from 2010 through 2021 in Denmark. We calculated the incidence and risk of colorectal cancer after bacteraemia with specific anaerobic bacteria using Escherichia coli bacteraemia as reference. RESULTS: Nationwide data on colorectal cancer and specific anaerobic bacteraemia (100% complete, representing 11,124 episodes). The frequencies of colorectal cancer within one year following anaerobic bacteraemia were higher for species, which almost exclusively reside in the colon, such as Phocaeicola vulgatus/dorei (5.5%), Clostridium septicum (24.2%), and Ruminococcus gnavus (4.6%) compared to 0.6% in 50,650 E. coli bacteraemia episodes. Bacteroides spp. had a subhazard ratio for colorectal cancer of 3.9 (95% confidence interval [CI], 3.0 to 5.1) and for Clostridium spp. it was 8.9 (95% CI, 6.7 to 11.8, with C. septicum 50.0 [95% CI, 36.0 to 69.5]) compared to E. coli (reference). CONCLUSION: This nationwide study identified specific colorectal cancer-associated anaerobic bacteria, which almost exclusively reside in the colon. Bacteraemia with these bacteria could be an indicator of colorectal cancer.

Staphylococcus aureus bacteraemia cases at Helen Joseph Hospital.

Background: Staphylococcus aureus bacteraemia (SAB) is associated with a high mortality. Data on SAB cases in South Africa (SA) are limited. Objectives: This study aimed to establish the demographic profile, risk factors and complications of patients with SAB in a tertiary inpatient setting. Method: We conducted a retrospective record review of inpatients above the age of 13 with SAB from October 2015 to November 2022 at Helen Jospeh Hospital (HJH) in Gauteng, SA. Results: A total of 126 patients with SAB were reviewed. The case fatality ratio among these patients was 20.6% (95% confidence interval [CI]: 13.9-28.8); this was similar for methicillin-sensitive S. aureus and methicillin-resistant S. aureus (p = 0.154). Almost half (49.2%) were community acquired, and these were chiefly associated with skin and soft tissue infections (45.2%), while most healthcare-associated community-acquired infections (18.3%) and nosocomial-related infections (32.5%) were associated with short-term venous catheterisation (40.6%). The most common risk factors for acquiring a SAB were prior hospitalisation in the last 90 days (27.8%), the presence of an invasive device (26.2%) and receipt of haemodialysis (15.1%). Having hypertension (adjusted odds ratio: 5.55 [95% CI: 1.31-23.55]) and being recently hospitalised (adjusted odds ratio: 11.88 [95% CI: 1.84-26.99]) were associated with statistically significant increased odds of death. Conclusion: SAB-associated all-cause mortality remains high in a middle-income tertiary hospital setting, albeit with a case fatality ratio comparable to that seen in high-income countries. Contribution: Our study suggests that acceptable outcomes are achievable in tertiary middle-income settings provided there is access to resources including infectious diseases consultation, echocardiograms and basic infection control practices.

Identifying organisms directly from BacT/Alert FAN plus blood culture bottles using Vitek MS in a state-wide laboratory network.

Identifying organisms directly from positive blood culture bottles using matrix-assisted laser desorption-ionisation time-of-flight mass spectrometry (MALDI-TOF MS) has many advantages to patients, clinical services, and laboratories. However, few published methods have demonstrated good performance using the current BioMérieux culture bottles and MALDI-TOF system: BacT/Alert FAN plus and Vitek MS. The effect of transporting bottles on test performance has not been assessed for any direct-from-bottle MS method. In this study, 802 positive blood culture bottles were analysed including 234 requiring inter-laboratory transport, using a method involving protein extraction with formic acid and acetonitrile. Correct identification rates were high for Staphylococcus aureus (58/58 of new diagnostic samples), Enterococcus faecalis (27/27), Gram-negative bacilli (160/176, 90.1%), and coagulase-negative Staphylococcus species (108/132, 81.8%). Three false identifications were made, none with clinical significance. For Gram-positive cocci in pairs or chains, more correct identifications were made from bottles analysed immediately compared to transported bottles (67% vs 44%, p=0.016), and longer transport time was associated with slightly lower probability of correct identification (OR 0.984 per additional hour, p=0.040). Transportation was not associated with a difference for other organism types. This technique is a vastly more cost-effective alternative to molecular techniques for rapid identification of bacteraemia isolates, and performance is minimally affected by inter-laboratory transport of bottles at ambient temperature.

A rare case of fatal rectal perforation and sepsis following traumatic urinary catheterization.

This case report details a fatal rectal perforation and sepsis in a comorbid 96-year-old male after traumatic urinary catheterization, highlighting the risks of IDC management in elderly patients with complex health backgrounds. Despite maximal medical therapy, including escalated antibiotics and ICU care, the patient died from septic shock linked to improper catheter insertion by a non-specialist nurse in the community. This case emphasizes the urgent need for better catheterization practices, specialized nursing education, and clear guidelines to prevent such outcomes.

Meta-meta-analysis of the mortality risk associated with MRSA compared to MSSA bacteraemia.

Staphylococcus aureus bacteraemia (SAB) is a bloodstream infection that carries a high risk of exacerbating a diseased state and may result in an increased death rate. The aim of this study was to assess mortality risk in Methicillin Resistant Staphylococcus aureus (MRSA) bacteraemia compared to Methicillin Susceptible Staphylococcus aureus (MSSA) bacteraemia through meta-meta-analyses. The study followed PRISMA guidelines, conducting a comprehensive search in Scopus, PubMed, and Google Scholar. It included full-text systematic reviews and meta-analyses comparing MRSA vs. MSSA bacteraemia, excluding reviews without data pooling and unclear selection criteria. Validity was assessed using QUOROM and AMSTAR. Edwards' Venn diagrams were used to visualized overlaps between primary studies. Aggregated odds ratio (OR) and risk ratios with 95% confidence intervals were calculated using the random-effect model. Heterogeneity was evaluated using the Higgins I2 statistic. The study included 3 meta-analysis studies, a total of 38,159 patients, with 9,056 having MRSA bacteraemia and 29,103 having MSSA bacteraemia. Data were collected from 46 different outcome studies published between 2001 and 2022. The meta-analyses used 7 to 33 primary studies from 1990 to 2020, with no overlap. Odds ratios (ORs) ranged from 1.78 to 2.92, while relative risks (RR) ranged from 1.57 to 2.37 for the included meta-anlysis. The pooled analysis confirmed a higher risk of mortality in patients with MRSA bacteraemia (OR: 2.35, RR: 2.01, HR: 1.61) compared to MSSA bacteraemia. Heterogeneity among the studies was considerable (I2: 90-91%). The study strongly supports that most patient deaths from SAB are linked to MRSA rather than MSSA. This highlights the significant public health problem posed by SAB, with difficult and often unsuccessful treatment leading to increased mortality and high healthcare costs.

Recurrent Infective Endocarditis of the Mitral Valve after Orthotopic Heart Transplantation.

Introduction: Orthotopic heart transplantation is the gold standard for the treatment of advanced heart failure in the absence of contraindications. Infective endocarditis is a rare complication in patients after heart transplantation. The treatment of endocarditis after heart transplantation is challenging since there is a need for ongoing immunosuppression. Case description: We present the case of a 51-year-old orthotopic heart transplant recipient enrolled in a chronic dialysis program, in whom we diagnosed and successfully treated recurrent infective endocarditis of the mitral valve caused by Enterococcus and Enterobacter species. Despite the complicated course of the disease, the treatment was successful. Conclusions: Recurrent infective endocarditis after heart transplantation can be treated successfully with a multidisciplinary approach and robust antimicrobial therapy. LEARNING POINTS: There is a high risk of bacteraemia and subsequent endocarditis in patients with recurrent catheter-related sepsis.The spectrum of bacteria causing endocarditis in patients after heart transplantation differs from that in the general population.Scrupulous targeted antibiotic treatment is warranted for the treatment of immunosuppressed patients with endocarditis.

Consensus document of the Spanish Society of Paediatric Infectious Diseases (SEIP) and the Spanish Society of Paediatric Intensive Care (SECIP) for the diagnosis and treatment of central venous catheter-related infections in paediatric care.

Intravascular devices are essential for the diagnostic and therapeutic approach to multiple diseases in paediatrics, and central venous catheters (CVCs) are especially important. One of the most frequent complications is the infection of these devices, which is associated with a high morbidity and mortality. These infections are highly complex, requiring the use of substantial resources, both for their diagnosis and treatment, and affect vulnerable paediatric patients admitted to high-complexity units more frequently. There is less evidence on their management in paediatric patients compared to adults, and no consensus documents on the subject have been published in Spain. The objective of this document, developed jointly by the Spanish Society of Paediatric Infectious Diseases (SEIP) and the Spanish Society of Paediatric Intensive Care (SECIP), is to provide consensus recommendations based on the greatest degree of evidence available to optimize the diagnosis and treatment of catheter-related bloodstream infections (CRBSIs). This document focuses on non-neonatal paediatric patients with CRBSIs and does not address the prevention of these infections.

Antimicrobial resistance surveillance of Bacteroides fragilis isolated from blood cultures, Europe, 2022 (ReSuBacfrag).

BACKGROUND: Bacteroides fragilis is the most frequent cause of anaerobic bacteraemia. Although recent data suggest a rise in antimicrobial resistance (AMR) of this and other anaerobic bacteria, surveillance remains limited due to a lack of both data availability and comparability. However, a newly introduced standardised method for antimicrobial susceptibility testing (AST) of anaerobic bacteria has made larger scale surveillance possible for the first time. AIM: To investigate phenotypic AMR of Bacteroides fragilis isolates from bacteraemia across Europe in 2022. METHODS: In a multicentre approach, clinical microbiology laboratories in Europe were invited to contribute results of AST for Bacteroides fragilis blood culture isolates (including only the first isolate per patient and year). AST of a selection of four antibiotics was performed locally by participating laboratories in a prospective or retrospective manner, using the new EUCAST disc diffusion method on fastidious anaerobe agar (FAA-HB). RESULTS: A total of 16 European countries reported antimicrobial susceptibilities in 449 unique isolates of Bacteroides fragilis from blood cultures in 2022. Clindamycin demonstrated the highest resistance rates (20.9%, range 0 - 63.6%), followed by piperacillin-tazobactam (11.1%, 0 - 54.5%), meropenem (13.4%, 0 - 45.5%), and metronidazole (1.8%, 0 - 20.0%), all with wide variation between countries. CONCLUSION: Considering that the mean resistance rates across Europe were higher than expected for three of the four anti-anaerobic antibiotics under surveillance, both local AST of clinically relevant isolates of Bacteroides fragilis and continued surveillance on an international level is warranted.

Mortality impact of further delays in active targeted antibiotic therapy in bacteraemic patients that did not receive initial active empiric treatment: Results from the prospective, multicentre cohort PROBAC.

OBJECTIVES: The early initiation of the empirical antibiotic treatment and its impact on mortality in patients with bacteraemia has been extensively studied. However, information on the impact of precocity of the targeted antibiotic treatment is scarce. We aimed to study the impact of further delay in active antibiotic therapy on 30-day mortality among patients with bloodstream infection who had not received appropriate empirical therapy. DESIGN: We worked with PROBAC cohort (prospective and compound by patients from 26 different Spanish hospitals). We selected a total of 1703 patients, who survived to day 2 without having received any active antibiotic therapy against the causative pathogen. RESULTS: The 30-day mortality was 14% (238 patients). The adjusted odds of mortality increased for every day of delay, from 1.53 (95% confidence interval (CI) 1.13-2.08) for day 3 or after to 11.38 (95% CI 7.95-16.38) for day 6 or after. CONCLUSION: We concluded that among patients who had not received active treatment within the first 2 days of blood culture collection, additional delays in active targeted therapy were associated with increased mortality. These results emphasize the importance of active interventions in the management of patients with bloodstream infections.

Intravenous fosfomycin for treatment of severe infections caused by carbapenem-resistant Acinetobacter baumannii: A multi-centre clinical experience.

BACKGROUND: Severe infections caused by carbapenem-resistant Acinetobacter baumannii (CRAB) have been reported increasingly over the past few years. Many in-vivo and in-vitro studies have suggested a possible role of intravenous fosfomycin for the treatment of CRAB infections. METHODS: This multi-centre, retrospective study included patients treated with intravenous fosfomycin for severe infections caused by CRAB admitted consecutively to four hospitals in Italy from December 2017 to December 2022. The primary goal of the study was to evaluate the risk factors associated with 30-day mortality in the study population. A propensity score matched analysis was added to the model. RESULTS: One hundred and two patients with severe infections caused by CRAB treated with an intravenous fosfomycin-containing regimen were enrolled in this study. Ventilator-associated pneumonia (VAP) was diagnosed in 59% of patients, primary bacteraemia in 22% of patients, and central-venous-catheter-related infection in 16% of patients. All patients were treated with a regimen containing intravenous fosfomycin, mainly in combination with cefiderocol (n=54), colistin (n=48) or ampicillin/sulbactam (n=18). Forty-eight (47%) patients died within 30 days. Fifty-eight (57%) patients experienced clinical therapeutic failure. Cox regression analysis showed that diabetes, primary bacteraemia and a colistin-containing regimen were independently associated with 30-day mortality, whereas adequate source control of infection, early 24-h active in-vitro therapy, and a cefiderocol-containing regimen were associated with survival. A colistin-based regimen, A. baumannii colonization and primary bacteraemia were independently associated with clinical failure. Conversely, adequate source control of infection, a cefiderocol-containing regimen, and early 24-h active in-vitro therapy were associated with clinical success. CONCLUSIONS: Different antibiotic regimens containing fosfomycin in combination can be used for treatment of severe infections caused by CRAB.

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 SAB. METHODS: We conducted a retrospective observational study of adults with SAB between 20/12/2019 and 23/08/2022 (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 bacteraemia, 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 vs. improve clinical response in patients with metastatic SAB.

Polymicrobial arcanobacterium haemolyticum intracerebral abscess: A case report and review of the literature.

Objective: This article describes a case of polymicrobial Arcanobacterium haemolyticum pharyngitis and sinusitis complicated by intracranial complications and reviews similar cases in the literature. Case summary: A 21-year-old immunocompetent male presented with symptoms of sore throat, rhinorrhoea, lethargy, headache, and rash. Imaging demonstrated sinusitis, pre-septal sinusitis, peritonsillar abscess formation, subdural empyema and cerebritis. He was managed with endoscopic sinus surgery, craniotomy for evacuation of subdural empyema and antibiotics. Microbiological samples demonstrated growth of A. haemolyticum, strep. anginosus, and fusobacterium necrophorum. He subsequently developed a cerebral abscess requiring stereotactic needle drainage. After a prolonged course of antibiotics, the patient was discharge and made a good recovery. Discussion: A. haemolyticum is an uncommon cause of non-streptococcal pharyngitis that may occur alongside other microorganisms and is rarely associated with severe intracranial complications. This organism and its antibiotic susceptibility patterns should be considered in complicated upper respiratory tract infections in immunocompetent hosts. Penicillins and macrolide antibiotics form the mainstay of therapy for A. haemolyticum.

Performance of Risk Scores in Predicting Infective Endocarditis in Patients with Staphylococcus aureus Bacteraemia in a Prospective Asian Cohort.

Background: Several risk scores have been derived to predict the risk of infective endocarditis (IE) amongst patients with Staphylococcus aureus bacteraemia (SAB), which helps to guide clinical management. Methods: We prospectively studied 634 patients admitted with SAB. The cohort was stratified into those with or without IE, and the PREDICT Day 1, Day 5 and VIRSTA scores were tabulated. Area under the receiver operating characteristic (AUC) curves were constructed to compare the performance of each score. Results: Of the 634 patients examined, 36 (5.7%) had IE. These patients were younger (51.6 ± 20.1 vs. 59.2 ± 18.0 years, p = 0.015), tended to have community acquisition of bacteraemia (41.7% vs. 17.9%, p < 0.001), and had persistent bacteraemia beyond 72 h (19.4% vs. 6.0%, p = 0.002). The VIRSTA score had the best performance in predicting IE (AUC 0.76, 95%CI 0.66-0.86) compared with PREDICT Day 1 and Day 5. A VIRSTA score of <3 had the best negative predictive value (97.5%), compared with PREDICT Day 1 (<4) and Day 5 (<2) (94.3% and 96.6%, respectively). Conclusions: Overall, the risk scores performed well in our Asian cohort. If applied, 23.5% of the cohort with a VIRSTA ≥ 3 would require TEE, and a score of <3 had an excellent negative predictive value.

Bloodstream Infection Caused by Erysipelothrix rhusiopathiae in an Immunocompetent Patient.

Erysipelothrix rhusiopathiae is a facultative anaerobe Gram-positive bacillus, which is considered a zoonotic pathogen. E. rhusiopathiae causes erysipeloid, mainly in occupational groups such as veterinarians, slaughterhouse workers, farmers, and fishermen. Two cutaneous forms (localised and generalised) and a septicaemic form have been described. Here, we report the isolation of a strain of E. rhusiopathiae from a 56-year-old immunocompetent obese male admitted to Fondazione IRCCS Policlinico San Matteo Pavia (Italy). Blood cultures were collected and Gram-positive bacilli were observed. E. rhusiopathiae grew and was identified. Antimicrobial susceptibility tests were performed and interpreted with EUCAST breakpoints (PK-PD). The strain was susceptible to all the antibiotics tested, while it was intrinsically resistant to vancomycin. The clinical diagnosis of E. rhusiopathiae can be challenging, due to the broad spectrum of symptoms and potential side effects, including serious systemic infections such as heart diseases. In the case described, bacteraemia caused by E. rhusiopathiae was detected in a immunocompetent patient. Bacteraemia caused by E. rhusiopathiae is rare in immunocompetent people and blood cultures were proven to be essential for the diagnosis and underdiagnosis of this pathogen, which is possible due to its resemblance to other clinical manifestations.

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.

Gingival Necrosis Related to Sepsis-Induced Agranulocytosis Due to Pseudomonas aeruginosa Bacteraemia: A Case Report.

Background: There have been no reports of sepsis-induced agranulocytosis causing gingival necrosis in otherwise medically healthy patients to the authors' best knowledge. Even though there are several case reports of gingival necrosis secondary to medication-induced agranulocytosis, they have not systematically described the natural progression of agranulocytosis-related gingival necrosis. Methods: This paper presents a case report of a 29-year-old female Indian patient with generalised gingival necrosis and constitutive signs of intermittent fever, nausea, and vomiting. She also complained of abdominal pains. Blood counts showed agranulocytosis, and the patient was admitted for a workup of the underlying cause. Parenteral broad-spectrum antibiotics were administered, which brought about clinical resolution. Results: Her gingival necrosis was attributed to sepsis-induced agranulocytosis triggered by Pseudomonas aeruginosa bacteraemia, and upon clinical recovery, spontaneous exfoliation left behind exposed bone. Secondary healing over the exposed alveolar bone was noted after a year-long follow-up, albeit with some residual gingival recession. Conclusions: Oral manifestations of gingival necrosis, when present with concomitant constitutive symptoms, could indicate a serious underlying systemic condition that could be potentially life-threatening if left untreated. Dentists should be cognizant of this possibility so that timely intervention is not delayed.

Apramycin efficacy against carbapenem- and aminoglycoside-resistant Escherichia coli and Klebsiella pneumoniae in murine bloodstream infection models.

BACKGROUND: The aminoglycoside apramycin has been proposed as a drug candidate for the treatment of critical Gram-negative systemic infections. However, the potential of apramycin in the treatment of drug-resistant bloodstream infections (BSIs) has not yet been assessed. METHODS: The resistance gene annotations of 40 888 blood-culture isolates were analysed. In vitro profiling of apramycin comprised cell-free translation assays, broth microdilution, and frequency of resistance determination. The efficacy of apramycin was studied in a mouse peritonitis model for a total of nine Escherichia coli and Klebsiella pneumoniae isolates. RESULTS: Genotypic aminoglycoside resistance was identified in 87.8% of all 6973 carbapenem-resistant Enterobacterales blood-culture isolates, colistin resistance was shown in 46.4% and apramycin in 2.1%. Apramycin activity against methylated ribosomes was > 100-fold higher than that for other aminoglycosides. Frequencies of resistance were < 10-9 at 8 × minimum inhibitory concentration (MIC). Tentative epidemiological cut-offs (TECOFFs) were determined as 8 µg/mL for E. coli and 4 µg/mL for K. pneumoniae. A single dose of 5 to 13 mg/kg resulted in a 1-log colony-forming unit (CFU) reduction in the blood and peritoneum. Two doses of 80 mg/kg resulted in an exposure that resembles the AUC observed for a single 30 mg/kg dose in humans and led to complete eradication of carbapenem- and aminoglycoside-resistant bacteraemia. CONCLUSION: Encouraging coverage and potent in vivo efficacy against a selection of highly drug-resistant Enterobacterales isolates in the mouse peritonitis model warrants the conduct of clinical studies to validate apramycin as a drug candidate for the prophylaxis and treatment of BSI.

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.

Short versus prolonged duration of therapy for Pseudomonas aeruginosa bacteraemia: a systematic review and meta-analysis.

The optimal duration of therapy for Pseudomonas aeruginosa bloodstream infection (PSA-BSI) is unknown, with prolonged therapy frequently favored due to severity of infection, patient complexity, risk of multi-drug resistance, and high mortality. We therefore conducted a systematic review and meta-analysis of studies with head-to-head comparison of short versus prolonged therapy for PSA-BSI. A comprehensive search including Ovid MEDLINE, Embase, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Scopus was performed. We pooled risk ratios using DerSimonian-Laird random effects model and performed subgroup analysis of outcomes including all-cause mortality, recurrent infection, and composite of these outcomes among patients receiving short versus prolonged therapy for PSA-BSI. Heterogeneity was assessed by the I2-index. Risk of bias for cohort studies was assessed using ROBINS-I tool. Of the 908 identified studies, six were included in the systematic review and five studies with head-to-head comparison of treatment duration were assessed in the meta-analysis, totalling 1746 patients. No significant difference in propensity score-weighted composite outcome (30-day all-cause mortality or recurrent infection) was noted between patients receiving short or prolonged therapy, with a pooled RR risk ratio of 0.80 (95% CI confidence interval 0.51-1.25, P=0.32; I2 = 0%). Additionally, duration of therapy did not impact individual outcomes of 30-day all-cause mortality or recurrent/persistent infection. Our meta-analysis demonstrated that short duration of antimicrobial therapy may have similar efficacy to prolonged treatment for PSA-BSI. Future randomized trials will be necessary to definitively determine optimal management of PSA bacteraemia.

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.