Ultrasonographic Findings of Catheter-Related Bloodstream Infection in Pediatric Patients.

BACKGROUND: Catheter removal is essential for treating catheter-related bloodstream infection (CRBSI); however, clinicians are sometimes hesitant to remove catheters in pediatric patients due to the difficulty of securing vascular access. Confirming the diagnosis of CRBSI is important to justify catheter removal. The purpose of this study was to describe the sonographic findings of CRBSI. MATERIALS AND METHODS: We included patients with a central venous catheter (CVC) or peripherally inserted central catheter (PICC) who had a positive blood culture and underwent ultrasound. The patients were classified as with or without CRBSI. Sonographic findings, such as the presence/absence of thrombus, venous wall thickening, hyperechogenicity, and fluid collection around the vein were compared using Fisher's exact test. RESULTS: Of the 58 patients, 38 (66%) were diagnosed with CRBSI. The presence of thrombus (19/38 vs 3/20, P = .011); and hyperechogenicity around the vein (14/38 vs 2/20, P = .035) differed significantly, but There was no significant difference in the presence of venous wall thickening (10/38 vs 1/20, P = .077), and fluid collection around the vein (5/38 vs 0/20, P = .153), did not differ significantly in patients with and without CRBSI, respectively. One-third of patients with CRBSI, including 11 (42.3%) patients with CVC, and 2 (16.7%) patients with PICC, did not have abnormal sonographic findings. CONCLUSION: Ultrasound findings are useful for diagnosing CRBSI. However, the sensitivity of sonographic findings is low and abnormal sonographic findings are sometimes absent in children with CRBSI; therefore, physicians should not rule out CRBSI based on normal sonographic findings, especially in patients a CVC and a positive blood culture.

Predictors of infectious foci on FDG PET/CT in Staphylococcus aureus bacteremia.

We looked for predicting factors for the detection of infectious foci on 18F-fluorodeoxyglucose-positron emission tomography in combination with computed tomography (FDG PET/CT) among patients with Staphylococcus aureus bacteremia (SAB) who participated in an interventional study that was conducted at Rambam Health Care Campus, between July 1, 2015 and February 1, 2019. The primary outcome was an infectious focus detected by FDG PET/CT. Independent predictors for detection of focal infection were identified using univariate followed by a logistic regression multivariate analysis. We included 149 patients with 151 separate episodes of SAB who underwent FDG-PET/CT. Focal infections were detected in 107 patients (70.8%). Independent predictors for focal infection detection were community acquisition of bacteremia with odds ratio (OR) 3.03 [95% confidence interval (CI) 1.04-8.77], p-0.042 and C reactive protein (CRP) with OR 1.09 [95% CI 1.04-1.14], p < 0.001. Primary bacteremia was inversely associated with focal infection detection with OR 0.27 [0.10-0.69], p = 0.007, as were the pre-scan blood glucose levels OR 0.9 [0.98-0.99], p-0.004. The latter stayed significant in the subgroup of patients with diabetes mellitus. To conclude, patients with community-acquired bacteremia or high CRP levels should be carefully investigated for focal infection. Patients who present with primary bacteremia seem to be at low risk for focal infection.

Importance of Blood Glucose Management Before 18F-FDG PET/CT in 322 Patients with Bacteremia of Unknown Origin.

We investigated the effects of blood glucose levels on the performance of 18F-FDG PET/CT for detecting an infection focus in patients with bacteremia. Methods: A total of 322 consecutive patients with bacteremia who underwent 18F-FDG PET/CT between 2010 and 2021 were included. Logistic regression analysis was performed to evaluate the association between finding a true-positive infection focus on 18F-FDG PET/CT and blood glucose level, type of diabetes, and use of hypoglycemic medication. C-reactive protein, leukocyte count, duration of antibiotic treatment, and type of isolated bacteria were considered as well. Results: Blood glucose level (odds ratio, 0.76 per unit increase; P = <0.001) was significantly and independently associated with 18F-FDG PET/CT outcome. In patients with a blood glucose level between 3.0 and 7.9 mmol/L (54-142 mg/dL), the true-positive detection rate of 18F-FDG PET/CT varied between 61% and 65%, whereas in patients with a blood glucose level between 8.0 and 10.9 mmol/L (144-196 mg/dL), the true-positive detection rate decreased to 30%-38%. In patients with a blood glucose level greater than 11.0 mmol/L (200 mg/dL), the true-positive detection rate was 17%. In addition to C-reactive protein (odds ratio, 1.004 per point increase; P = 0.009), no other variables were independently associated with 18F-FDG PET/CT outcome. Conclusion: In patients with moderate to severe hyperglycemia, 18F-FDG PET/CT was much less likely to identify the focus of infection than in normoglycemic patients. Although current guidelines recommend postponing 18F-FDG PET/CT only in cases of severe hyperglycemia with glucose levels greater than 11 mmol/L (200 mg/dL), a lower blood glucose threshold seems to be more appropriate in patients with bacteremia of unknown origin and other infectious diseases.

Impact of 18F-FDG-PET/CT on the management of Staphylococcus aureus bacteraemia: a retrospective observational study.

OBJECTIVES: To assess the impact of 18F-FDG-PET/CT on the diagnosis and management of patients with Staphylococcus aureus bacteraemia (SAB). METHODS: Post hoc analysis of a prospective cohort of consecutive adult patients diagnosed with SAB (January 2013-December 2017). Patients who underwent 18F-FDG-PET/CT at the discretion of the attending physician were included. Endpoints were the identification of previously unknown infectious foci and changes in clinical management, defined as changes in the duration or class of antibiotic therapy, a surgical procedure on the source of infection or a change in the decision to remove or retain an implantable device. RESULTS: We included 39 patients (median age: 69 years, IQR:60-79). Fifteen (39%) patients did not have an infectious focus identified before 18F-FDG-PET/CT). Thirty new infectious foci were detected in 22/39 (56%) patients. In 11/15 (73%) patients without an identified focus at least one infectious focus was detected by 18F-FDG-PET/CT. In 22/26 (85%) patients with implantable devices, 18F-FDG-PET/CT confirmed or ruled out infection or detected local complications. Out of 13 device infections, 10 were detected by 18F-FDG-PET/CT (7/10 for the first time). In 19/39 (49%) patients 18F-FDG-PET/CT results led to changes in clinical management (15 changes in antibiotic therapy, 2 device removals, 2 surgical procedures, 1 avoidance of a surgical procedure). CONCLUSIONS: 18F-FDG-PET/CT may be a useful asset in the management of selected SAB cases, allowing the identification of previously undetected infectious foci and optimization of therapy, particularly in patients with endovascular devices. Indication should be made on a case-by-case basis.

Evidence of Clinical Impact Supports a New Petition for Medicare Coverage of 2-[18F]Fluoro-2-Deoxy-D-Glucose Positron Emission Tomography/Computed Tomography in the Evaluation of Staphylococcus aureus Bacteremia: A Focused Literature Review and Call to Action.

Staphylococcus aureus bacteremia (SAB) causes considerable morbidity and mortality and requires comprehensive assessment for metastatic infection. The roles of routine imaging beyond echocardiography in SAB, including 2-[18F]fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography (18F-FDG-PET/CT), remain contentious. We performed a literature review of studies reporting impact of 18F-FDG-PET/CT on the clinical management or outcomes of SAB published through 1 March 2022. We identified 7 observational studies in which 18F-FDG-PET/CT frequently identified metastatic foci of infection, revealed foci undetected by prior investigations, led to additional source control procedures, and was associated with fewer infection relapses and lower mortality. Calculated numbers needed to treat for receipt of 18F-FDG-PET/CT were 7-9 to change antimicrobial therapy, 10-27 to lead to an additional source control procedure, and 4-8 to prevent death. These data are comparable to the evidence for clinical impact of other diagnostic modalities accepted as standard of care in SAB, and form a compelling basis for advocacy to expand access to 18F-FDG-PET/CT.

[18F]FDG-PET/CT in Staphylococcus aureus bacteremia: a systematic review.

OBJECTIVES: [18F]FDG-PET/CT is used for diagnosing metastatic infections in Staphylococcus aureus bacteremia (SAB) and guidance of antibiotic treatment. The impact of [18F]FDG-PET/CT on outcomes remains to be determined. The aim of this systematic review was to summarize the effects of [18F]FDG-PET/CT on all-cause mortality and new diagnostic findingsin SAB. METHODS: We systematically searched PubMed, EMBASE.com, Web of Science, and Wiley's Cochrane library from inception to 29 January 2021. Eligible studies were randomized controlled trials, clinically controlled trials, prospective and retrospective cohort studies, and case-control studies investigating the effects of [18F]FDG-PET/CT in hospitalized adult patients with SAB. We excluded studies lacking a control group without [18F]FDG-PET/CT. Risk of bias was assessed using the ROBINS-I tool and certainty of evidence using the GRADE approach by two independent reviewers. RESULTS: We identified 1956 studies, of which five were included in our qualitative synthesis, including a total of 880 SAB patients. All studies were non-randomized and at moderate or serious risk of bias. Four studies, including a total of 804 patients, reported lower mortality in SAB patients that underwent [18F]FDG-PET/CT. One study including 102 patients reported more detected metastatic foci in the participants in whom [18F]FDG-PET/CT was performed. DISCUSSION: We found low certainty of evidence that [18F]FDG-PET/CT reduces mortality in patients with SAB. This effect is possibly explained by a higher frequency of findings guiding optimal antibiotic treatment and source control interventions.

Bedside ultrasound as a screening test for the diagnosis of catheter-related bloodstream infection (CRBI).

PURPOSE: Between 15 and 30% of all nosocomial bacteremias and sepsis are associated with the use of intravascular devices. Catheter-related bloodstream infections (CRBI) are infections in which the organism identified in the blood is also present on the tip of the catheter itself or in a blood sample taken through it. The aim of the study was to evaluate the role of ultrasound in the diagnosis of infections related to the use of central catheters. METHODS: Between January 2018 and June 2019, we carried out a prospective study on 36 patients with a central catheter, such as a central venous catheter (CVC), a central catheter with peripheral insertion (PICC), or a fully implanted central venous catheter (PORT-a-cath) and who had signs and symptoms of infection. These patients were submitted to an ultrasound of the catheter upon arrival in the ward in case of suspected infection, or at the time of the onset of signs and symptoms of infection (if these arose during hospitalization). Patients with a central catheter but without signs and symptoms of infection were not included in the study. The end point of the study was to evaluate sensitivity (SENS), specificity (SPEC), positive and negative predictive value (PPV-NPV) and overall diagnostic accuracy (ODA) of ultrasound in the diagnosis of CRBI through Receiver Operating Characteristic (ROC) curve analysis. RESULTS: US showed a SENS of 94%, a SPEC of 84%, a PPV of 84%, an NPV of 94% and an ODA of 88.8% for the diagnosis of CRBI. CONCLUSIONS: Preliminary data from our study show that US of intravascular devices has a high SENS and SPEC in the diagnosis of CRBI, and can, therefore, be used as a valid tool to decide whether to remove the device early or leave it in place.

Central venous catheter insertion: Review of recent evidence.

Guidelines for prevention of catheter-related bloodstream infection (CR-BSI) describe a series of recommendations for correct insertion and handling of central venous catheters (CVCs). Since their implementation, quality programs such as "Zero bacteremia" have achieved a reduction in CR-BSI rates, but there is still room for further improvement. New evidence is emerging regarding, e.g., antiseptic-antimicrobial impregnated catheters or the use of passive disinfection of closed connectors. These examples of new tools among others might help to further decrease infection rates. This article aims to review new evidence-based strategies to reduce catheter insertion-related infection.

Forgoing transesophageal echocardiogram in selected patients with complicated Staphylococcus aureus bacteremia.

Infective endocarditis (IE) has been increasingly recognized as an important complication of Staphylococcus aureus bacteremia (SAB), leading to a low threshold for echocardiography and extended treatment with anti-staphylococcal agents. However, outside of IE, many indications for prolonged anti-staphylococcal therapy courses are present. We sought to determine the frequency in which findings from a transesophageal echocardiogram (TEE) changed clinical SAB management in a large Canadian health region. Residents (> 18 years) with SAB from 2012 to 2014 who underwent transthoracic echocardiogram (TTE) and TEE were assessed. Patients potentially benefiting from an extended course of anti-staphylococcal agents were defined a priori. Patient demographics, treatment (including surgical), and clinical outcomes were extracted and evaluated. Of the 705 episodes of SAB that underwent a screening echocardiogram, 203 episodes underwent both a TTE and TEE, of which 92.1% (187/203) contained an a priori indication for extended anti-staphylococcal therapy. Regardless of TEE results, actual duration of therapy did not differ in SAB episodes that had ≥ 1 extended anti-staphylococcal therapy criteria (36.7 days, IQR 23.4-48.6 vs. 43.8 days, IQR 33.3-49.5, p = 0.17). Additionally, there were no cases in which TEE was utilized as the sole reason to shorten duration of therapy or proceed to surgery for those with SAB. Routine performance of TEE may be unnecessary in all SAB as many patients have pre-existing indications for extended anti-staphylococcal therapy independent of TEE findings. An algorithm to selectively identify cases of SAB that would benefit from TEE can reduce resource and equipment expenditure and patient risks associated with TEE.

Clinical implications of increased uptake in bone marrow and spleen on FDG-PET in patients with bacteremia.

PURPOSE: To investigate which clinical factors and laboratory values are associated with high FDG uptake in the bone marrow and spleen on 2-deoxy-2-[18F]fluoro-D-glucose (FDG) positron emission tomography (PET)/computed tomography (CT) in patients with bacteremia. METHODS: One hundred forty-five consecutive retrospective patients with bacteremia who underwent FDG-PET/CT between 2010 and 2017 were included. Mean standard uptake values (SUVmean) of FDG in bone marrow, liver, and spleen were measured. Bone marrow-to-liver SUV ratios (BLR) and spleen-to-liver SUV ratios (SLR) were calculated. Linear regression analyses were performed to examine the association of BLR and SLR with age, gender, hemoglobin, leukocyte count, platelets, glucose level, C-reactive protein (CRP), microorganism, days of antibiotic treatment before FDG-PET/CT, infection focus, use of immunosuppressive drugs, duration of hospital stay (after FDG-PET/CT), ICU admission, and mortality. RESULTS: C-reactive protein (p = 0.006), a cardiovascular or musculoskeletal focus of infection (p = 0.000 for both), and bacteremia caused by Gram-negative bacteria (p = 0.002) were independently and positively associated with BLR, while age (p = 0.000) and glucose level before FDG-PET/CT (p = 0.004) were independently and negatively associated with BLR. For SLR, CRP (p = 0.001) and a cardiovascular focus of infection (p = 0.020) were independently and positively associated with SLR, while age (p = 0.002) and glucose level before FDG-PET/CT (p = 0.016) were independently and negatively associated with SLR. CONCLUSION: High FDG uptake in the bone marrow is associated with a higher inflammatory response and younger age in patients with bacteremia. In patients with high FDG uptake in the bone marrow, a cardiovascular or musculoskeletal focus of infection is more likely than other foci, and the infection is more often caused by Gram-negative species. High splenic FDG uptake is associated with a higher inflammatory response as well, and a cardiovascular focus of infection is also more likely in case of high splenic FDG uptake.

Ruptured cerebral mycotic aneurysm in a left ventricular assist device patient with bacteremia.

A 50-year-old male with a history of nonischemic dilated cardiomyopathy presented in cardiogenic shock and ultimately underwent durable left ventricular assist device implantation. He recovered well initially but developed persistent bacteremia. His indwelling pacemaker leads were extracted due to evidence of vegetation. Shortly thereafter, around 3 months post-left ventricular assist device, he succumbed to a massive intracranial hemorrhage due to ruptured cerebral mycotic aneurysm. This case highlights the potential importance of brain imaging in left ventricular assist device patients with persistent bacteremia to avoid this likely catastrophic complication.

Prognostic Role of Left Ventricular Systolic Function Measured by Speckle Tracking Echocardiography in Septic Shock.

BACKGROUND: Left ventricular (LV) systolic dysfunction is common in septic shock. Global longitudinal strain (GLS) measured by speckle tracking echocardiography (STE) is a useful marker of intrinsic left ventricular systolic function. However, the association between left ventricular GLS and outcome in septic patients is not well understood. We performed this prospective study to investigate the prognostic value of LV systolic function utilizing speckle tracking echocardiography in patients with septic shock. METHODS: All the patients with septic shock based on sepsis-3 definition admitted to the intensive care unit were prospectively studied with STE within 24 hours after the onset of septic shock. Baseline clinical and echocardiographic variables were collected. The primary outcome was in-hospital mortality. RESULTS: During a 19-month period, 90 consecutive patients were enrolled in the study. The in-hospital mortality rate was 43.3%. Compared with survivors, nonsurvivors exhibited significantly less negative GLS (-13.1 ± 3.3% versus -15.8 ± 2.9%; p < 0.001), which reflected worse LV systolic function. The area under the ROC curves of GLS for the prediction of mortality was 0.76 (95% CI 0.67 to 0.87). Patients with GLS > -14.1% showed a significantly higher mortality rate (67.7% versus 15.6%; p < 0.0001; log-rank = 23.3; p < 0.0001). In the multivariate analysis, GLS (HR, 1.27; 95% CI 1.07 to 1.50, p = 0.005) and SOFA scores (HR, 1.27; 95% CI 1.08 to 1.50, p = 0.004) were independent predictors of in-hospital mortality. CONCLUSIONS: Our study indicated that LV systolic function measured by STE might be associated with mortality in patients with septic shock.

Bacteraemia after leadless pacemaker implantation.

BACKGROUND: Transvenous 3 permanent pacemaker-related infection is a severe condition associated with significant morbidity and mortality. Leadless pacemakers may be more resistant to bacterial seeding during bloodstream infection because of its small surface area and encapsulation in the right ventricle. This study reports the incidence and outcomes of bacteraemia in patients implanted with a Micra leadless pacemaker. We present 18 F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) findings obtained in a subgroup of patients. METHODS: We report a retrospective cohort study of 155 patients who underwent a Micra TPS implant procedure at the University Hospitals of Leuven between July 2015 and July 2019. We identified the patients who developed an episode of bacteraemia, proved by ≥2 positive blood cultures. RESULTS: Of the 155 patients, 15 patients presented an episode of bacteraemia at a median of 226 days (range: 3-1129) days after the implant procedure. Gram-positive species accounted for 73.3% (n = 11) of the bacteraemia including Staphylococcus (n = 5), Enterococcus (n = 3), and Streptococcus (n = 3). The source of infection was identified in nine patients (60%) including endocarditis in four patients, urinary tract in three patients, and skin in two patients. 18 F-FDG PET/CT imaging performed in six patients did not show sign of infection around the leadless pacemaker. Bacteraemia was resolved in all patients after adequate antibiotherapy. Four patients died early during follow up. For all other patients, there were no recurrence of systemic infection during a median follow up of 263 days (range: 15-1134). CONCLUSION: In our small cohort, no leadless pacemaker endocarditis was observed among patients with bacteraemia.

FDG-PET/CT in Fever of Unknown Origin, Bacteremia, and Febrile Neutropenia.

Fever of unknown origin, bacteremia, and febrile neutropenia are diagnostic challenges. FDG-PET/CT is a well-established modality in infection imaging and the literature increasingly supports its use in these settings. In fever of unknown origin, FDG-PET/CT is helpful, but diagnostic yield depends on patient selection and inflammatory markers. In bacteremia, FDG-PET/CT is cost-effective, reduces morbidity and mortality, and impacts treatment strategy. Although use of FDG-PET/CT in these domains is not established as part of a definitive diagnostic strategy, FDG-PET/CT may help establish final diagnosis in a difficult population and should be considered early in the diagnostic process.

Imaging in the investigation and management of Staphylococcus aureus bacteraemia: a role for advanced imaging techniques.

Staphylococcus aureus bacteraemia (SAB) continues to affect ∼25,000 patients in the UK per year with a high crude mortality of 30% at 90 days. Prompt source control improves outcomes in sepsis and SAB and is included in sepsis guidelines. A recent clinical trial of adjunctive antibiotic treatment in SAB found that the majority of recurrences of SAB were associated with a failure of source management. In this condition, the ability to control the source of infection may be limited by the ability to detect a focus of infection. Echocardiogram is now a routinely used tool to detect such unknown foci in the form of unexpected infectious vegetations. We review the literature to explore the utility of advanced imaging techniques, such as [18F]fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) and magnetic resonance imaging (including whole-body MRI), to detect foci which may otherwise be missed. As unknown foci are associated with increased mortality, we propose that increasing the detection of foci could enable improved source control and result in improved outcomes in SAB.

Development of a Staphylococcus aureus reporter strain with click beetle red luciferase for enhanced in vivo imaging of experimental bacteremia and mixed infections.

In vivo bioluminescence imaging has been used to monitor Staphylococcus aureus infections in preclinical models by employing bacterial reporter strains possessing a modified lux operon from Photorhabdus luminescens. However, the relatively short emission wavelength of lux (peak 490 nm) has limited tissue penetration. To overcome this limitation, the gene for the click beetle (Pyrophorus plagiophtalamus) red luciferase (luc) (with a longer >600 emission wavelength), was introduced singly and in combination with the lux operon into a methicillin-resistant S. aureus strain. After administration of the substrate D-luciferin, the luc bioluminescent signal was substantially greater than the lux signal in vitro. The luc signal had enhanced tissue penetration and improved anatomical co-registration with infected internal organs compared with the lux signal in a mouse model of S. aureus bacteremia with a sensitivity of approximately 3 × 104 CFU from the kidneys. Finally, in an in vivo mixed bacterial wound infection mouse model, S. aureus luc signals could be spectrally unmixed from Pseudomonas aeruginosa lux signals to noninvasively monitor the bacterial burden of both strains. Therefore, the S. aureus luc reporter may provide a technological advance for monitoring invasive organ dissemination during S. aureus bacteremia and for studying bacterial dynamics during mixed infections.

Procalcitonin and C-Reactive Protein As Markers of Bacteremia in Patients With Febrile Neutropenia Who Receive Chemotherapy for Acute Leukemia: A Prospective Study From Nepal.

PURPOSE: The purpose of this study was to evaluate the clinical significance of the biomarkers procalcitonin (PCT) and C-reactive protein (CRP) in patients with febrile neutropenia (FN) undergoing chemotherapy for acute leukemia. METHODS: We conducted a prospective, observational study in patients who developed FN while undergoing chemotherapy for acute leukemia. PCT and CRP were obtained in patients who presented with FN. Blood cultures also were obtained. The primary goals were to evaluate the ability of PCT and CRP to predict bacteremia in patients with FN. The secondary goals were to assess the prognostic role of PCT and CRP and to assess the microbiologic profile and culture sensitivity patterns in the study population. RESULTS: A total of 124 episodes of FN that involved 67 patients with acute leukemia occurred in the study. PCT was superior to CRP in the prediction of bacteremia. The median PCT level in the bacteremia group was 3.25 ng/mL compared with 0.51 ng/mL in the group without bacteremia (P < .01). The median values of CRP in the bacteremia and without-bacteremia groups were 119.3 mg/L and 94.5 mg/L, respectively (P = .07). There were no differences in median PCT and CRP in patients who died and those who improved. Of the 42 positive cultures, Gram-negative bacteremia was common (86%), and Escherichia coli was the most frequent organism isolated. Carbapenem resistance was seen in 39% of positive cultures. CONCLUSION: PCT is an effective biomarker to predict bacteremia in patients with FN undergoing chemotherapy for acute leukemia.