The comparative accuracy of pooled vs. individual blood culture sampling methods for diagnosis of catheter-related bloodstream infection.

BACKGROUND: Catheter-related bloodstream infection (CRBSI) is associated with increased morbidity, mortality, and cost of treatment in critically ill patients. A differential time to positivity (DTP) of 120 min or more between blood cultures obtained through the catheter vs. peripheral vein is an indicator of CRBSI with high sensitivity and specificity. However, it is no clear whether pooled sampling would be as efficient as individual sampling in order to reduce costs, contamination, or anemia. METHODS: This was a prospective diagnostic study conducted at the medical ICU and semi-ICU of Khon Kaen University's Srinagarind Hospital in Thailand from May 2020 to November 2021. Fifty patients with triple-lumen central venous catheters (CVCs) who were clinically suspected of CRBSI were enrolled. 15 mL of blood was drawn through each catheter lumen, 10 mL of which was inoculated into three blood culture bottles, and the remaining 5 mL was pooled into a single bottle. Sensitivity, specificity, accuracy, and time to positivity of the pooled blood cultures were calculated using individual blood cultures as a reference. RESULTS: Of the 50 patients enrolled, 14 (28%) were diagnosed with CRBSI, 57.9% of whom were infected with gram-negative bacteria as the causative pathogen (57.9%). Extensively drug-resistant (XDR) Klebsiella pneumoniae was the most common organism. Sensitivity and specificity of the pooled blood sampling method were 69.23% (95% CI [0.44-0.94]) and 97.3% (95% CI [0.92-1.02]), respectively. The area under the ROC curve (AUC) was 0.83 (95% CI [0.68-0.99]). A paired T-Test to compare time to positivity of the pooled blood bottle and the first positive culture from the individual bottles indicated statistical significance (14.9 and 12.4 h, respectively). The mean difference was 2.5 [0.9-4.1] h, with a 95% CI and a p-value of 0.006. CONCLUSION: Pooled blood sampling results in a lower sensitivity and longer time to positivity for CRBSI diagnosis in patients with triple-lumen CVCs than individual lumen sampling. Trial registration Retrospectively registered at Thai Clinical Trials Registry. The study was reviewed and approved on 08/03/2022. TCTR identification number is TCTR20220308002.

Diagnostic usefulness of differential time to positivity in neutropenic cancer patients with suspected catheter-related candidemia.

Methods for distinguishing catheter-related candidemia (CRC) from non-CRC before catheter removal remain limited. We thus evaluated the diagnostic performance of differential time to positivity (DTP) to diagnose CRC in neutropenic cancer patients with suspected CRC. Of the 35 patients enrolled, 15 (43%) with CRC (six definite and nine probable) and 17 (49%) with non-CRC were finally analyzed. Based on the receiver operating characteristic curve, the optimal cutoff value of DTP for diagnosing CRC was ≥1.45 hours with the sensitivity 80% (95% confidence interval [CI], 51-95) and specificity 100% (95% CI, 80-100), respectively.

Time to and differential time to blood culture positivity for assessing catheter-related yeast fungaemia: A longitudinal, 7-year study in a single university hospital.

BACKGROUND: Time to positivity (TTP) and differential time to positivity (DTTP) between central and peripheral blood cultures are commonly used for bacteraemia to evaluate the likelihood of central venous catheter (CVC)-related bloodstream infection. Few studies have addressed these approaches to yeast fungaemia. OBJECTIVES: This study aimed to evaluate TTP and DTTP to assess CVC-related yeast fungaemia (CVC-RYF). PATIENTS/METHODS: We retrospectively analysed the results from 105 adult patients with incident fungaemia, with CVC removed and cultured, collected from 2010 to 2017. The bottles were incubated in a BioMérieux BacT/ALERT 3D and kept for at least 5 days. RESULTS: Of the 105 patients included, most were oncology patients (85.7%) and had of long-term CVC (79.6%); 32 (30.5%) had a culture-positive CVC (defined as CVC-RYF) with the same species as in blood culture, and 69.5% had culture-negative CVC (defined as non-CVC-RYF, NCVC-RYF). Candida albicans represented 46% of the episodes. The median TTP was statistically different between CVC-RYF and NCVC-RYF (16.8 hours interquartile range (IQR) [9.7-28.6] vs 29.4 hours [IQR 20.7-41.3]; P = .001). A TTP <10 hours had the best positive likelihood ratio (21.5) for CVC-RYF, although the sensitivity was only 28%. DTTP was available for 52 patients. A DTTP >5 hours had a sensitivity of 100% and a specificity of 71% for CVC-RYF. CONCLUSIONS: Since the median TTP was 17 hours and the most performing DTTP >5 hours, these delays are too long to take a decision in the same operational day. More rapid methods for detecting infected catheters should be tested to avoid unnecessary CVC withdrawal.

Importance of blood cultures from peripheral veins in pediatric patients with cancer and a central venous line.

BACKGROUND: When an infection is suspected in a child with cancer and a central venous line (CVL), cultures are often only obtained from the CVL and not from a peripheral vein (PV). This study was undertaken to evaluate the importance of concomitant blood cultures from the CVL and a PV. PROCEDURE: Clinical data and the results of all cultures taken concomitantly from the CVL and a PV were registered prospectively in children admitted with fever from April 2008 to December 2012 at the Department of Pediatrics at Aarhus University Hospital Skejby. RESULTS: During the study period 654 paired cultures obtained from the CVL and from a PV within two hour of each other were included. A true bloodstream infection (BSI) was registered in 112 episodes. In 20 (17%) out of 112, true BSI growth of a microorganism was detected only in the culture from a PV including seven cases of Escherichia coli and three cases of Staphylococcus aureus. In 52 episodes the same microorganism was cultured from both the CVL and a PV. Twenty-four of these episodes were classified as catheter-related bloodstream infections (CRBSI) using differential time to positivity. In total, 64 (57%) of all true BSI were defined as CRBSI. CONCLUSIONS: Blood cultures should be obtained from a PV in addition to cultures from CVL at the onset of fever in pediatric patients with cancer in order to maximize the findings of true BSIs. The frequency of CRBSI may be over-estimated if blood cultures are drawn from CVL only.

Clinical Outcome of Patients with Escherichia coli Isolated from Catheter Lumens and/or Peripheral Blood Cultures: A Retrospective Analysis.

BACKGROUND: Escherichia coli commonly causes catheter-related bloodstream infection (C-RBSI) in specific populations. The differential time to positivity (DTTP) technique is the recommended conservative procedure for diagnosing C-RBSIs. METHODS: We conducted a retrospective study of episodes in which E. coli was isolated from catheter lumens obtained using the DTTP technique. Microbiological and clinical data were obtained based on the DTTP technique as either catheter colonization, C-RBSI, or non-C-RBSI. RESULTS: A total of 89 catheter blood cultures were included, classified as follows: catheter colonization, 33.7%; C-RBSI, 9.0%; and non-C-RBSI, 57.3%. Only 15.7% of the catheters were withdrawn, with no positive catheter-tip cultures. We found no statistically significant differences in catheter type, antibiotic treatment, or clinical outcome among the groups, except for the frequency of catheter lock therapy or in the frequency of successful treatment. Mortality was associated with C-RBSI in only one patient. CONCLUSION: E. coli bacteremia diagnosed by the DTTP technique was classified as non-catheter-related in most patients. As the majority of the catheters were retained, E. coli bacteremia could not be microbiologically confirmed as catheter-related by the catheter-tip culture. Future studies are needed to assess the profitability of the DTTP technique for diagnosing E. coli C-RBSIs.

Understanding the diagnosis of catheter-related bloodstream infection: real-time monitoring of biofilm growth dynamics using time-lapse optical microscopy.

Background: The differential time to positivity (DTTP) technique is recommended for the conservative diagnosis of catheter-related bloodstream infection (C-RBSI). The technique is based on a 120-minute difference between microbial growth in blood drawn through the catheter and blood drawn through a peripheral vein. However, this cut-off has failed to confirm C-RBSI caused by Candida spp. and Staphylococcus aureus. Objective: We hypothesized that the biofilm of both microorganisms disperses faster than that of other microorganisms and that microbial load is rapidly equalized between catheter and peripheral blood. Therefore, our aim was to compare the biofilm dynamics of various microorganisms. Methods: Biofilm of ATCC strains of methicillin-resistant Staphylococcus epidermidis, methicillin-susceptible S. aureus, Enterococcus faecalis, Escherichia coli and Candida albicans was grown on silicon disks and analyzed using time-lapse optical microscopy. The time-lapse images of biofilms were processed using ImageJ2 software. Cell dispersal time and biofilm thickness were calculated. Results: The mean (standard deviation) dispersal time in C. albicans and S. aureus biofilms was at least nearly 3 hours lower than in biofilm of S. epidermidis, and at least 15 minutes than in E. faecalis and E. coli biofilms. Conclusion: Our findings could explain why early dissemination of cells in C. albicans and S. aureus prevents us from confirming or ruling out the catheter as the source of the bloodstream infection using the cut-off of 120 minutes in the DTTP technique. In addition, DTTP may not be sufficiently reliable for E. coli since their dispersion time is less than the cut-off of 120 minutes.

Diagnostic and Therapeutic Utility of Positive Intravascular Catheter Tip Cultures.

This study evaluated the performance and clinical utility of performing intravascular catheter tip cultures (CTC). A retrospective chart review was conducted over a 2.5 year period on all patients who demonstrated growth of at least one organism on CTC. There were a total of 391 CTC performed. 88 (23%) grew at least one organism, while 303 (77%) had no growth. Of the positive CTC, 81 (92%) had blood cultures (BC) collected within 14 days, whereas 7 (8%) did not. Of the positive CTC with BC, 67 (83%) were BC-positive, whereas 14 (17%) were negative. For cases with growth on both CTC and BC, the organisms identified were concordant for 46 (69%) cases and discordant for 21 (31%). Of the concordant cases, 43 (93%) were clinically considered to be bacterial bloodstream infections that were secondary to a catheter infection. For all of the positive CTC cases total, there was no change in the antibiotics or management, with the exceptions of 2 out of 88 (2%) cases. Catheters were removed and cultured for an average of 38.6 h (range: -98 to 288 h) after positive BC results were available. Most CTC are negative, and for the CTC that are positive, most are concordant with BC results. CTC results are generally only available several days after positive BC results are known. The CTC results did not alter the antibiotic therapy or management, with the exceptions of rare cases. As such, this study concludes that CTC do not contribute diagnostic or therapeutic value. Therefore, current guidelines by the Infectious Diseases Society of America on catheter-related bloodstream infection diagnosis should be revised to exclude CTC collection. IMPORTANCE In patients with intravascular catheters who are febrile or have positive blood cultures and no other obvious sources of infection, catheter tip cultures are often obtained to evaluate potential catheter-related bloodstream infections. However, previous studies reported that the management of catheter-related bloodstream infection cases is entirely based on blood culture growth and susceptibilities and that catheter tip cultures have low diagnostic positive predictive value. Our study represents the largest contemporary evaluation that includes chart reviews on all positive catheter tip culture cases. We found that positive cultures led to no changes in antibiotics or management, except for in two cases. Furthermore, 92% of positive catheter tip cultures were associated with blood culture collections, and catheter cultures were generally available only several days after the blood culture results were known. Thus, our study supports the claim that positive catheter tip cultures add limited diagnostic and therapeutic value in suspected catheter-related bloodstream infections.

Prospective clinical study on the incidence of catheter-related complications in a neurological intensive care unit: 4 years of experience.

INTRODUCTION: Over the past decades, significant efforts have been made to reduce early and late catheter-related complications in critically ill patients, using approaches based on bundles of evidence-based interventions. METHODS: In this prospective clinical study, the authors evaluated the incidence of catheter-related complications in their neuro-intensive care unit during a 4-year period, adopting systematically the GAVeCeLT bundles for the insertion and management of all central venous access devices: centrally inserted central catheters (CICCs), peripherally inserted central catheters (PICCs) and femorally inserted central catheters (FICCs). All early/immediate and late complications were recorded. RESULTS: On 486 central lines (328 CICCs, 149 PICCs and 9 FICCs), the only clinically relevant early/immediate complication was primary tip malposition (1%). In regards late infective complications, the authors did not record any case of catheter-related bloodstream infection; though, they observed one case of central line associated blood stream infection (one CICC; 0.14/1000 catheter days), and 15 cases of catheter colonization (12 CICCs and 3 PICCs; 2.09 episodes/1000 catheter days). Late non-infective complications were few: 14 accidental dislodgments (2.9%), 18 irreversible lumen occlusions (3.7%), and no episodes of symptomatic catheter-related thrombosis or tip migration. CONCLUSION: The systematic adoption of the GAVeCeLT bundles for CVAD insertion and maintenance was associated with a minimization of catheter-related complications. The strict adherence to the recommendations included in these bundles was the major determinant for clinical success.

Performance of differential time to positivity as a routine diagnostic test for catheter-related bloodstream infections: a single-centre experience.

OBJECTIVE: To assess the performance of differential time to positivity (DTP) for the diagnosis of catheter-related bloodstream infections (CRBSI). METHODS: From all episodes of bloodstream infections (BSI) diagnosed during a 15-year period (2003-17) those in which a paired set of blood cultures drawn from a catheter and a peripheral vein were positive for the same microorganism and had a clinically and/or microbiologically defined source were selected. To assess diagnostic discrimination ability and accuracy of DTP for CRBSI, area under the receiver operating characteristic curves (AUC) and performance characteristics of a DTP ≥2 h were computed. RESULTS: A total of 512 BSI were included, of which 302 (59%) were CRBSI. Discrimination ability of DTP was low for Staphylococcus aureus (AUC 0.656 ± 0.06), coagulase-negative staphylococci (AUC 0.618 ± 0.081), enterococci (AUC 0.554 ± 0.117) and non-AmpC-producing Enterobacteriaceae (AUC 0.653 ± 0.053); moderate for Pseudomonas aeruginosa (AUC 0.841 ± 0.073), and high for AmpC-producing Enterobacteriaceae (AUC 0.944 ± 0.039). For the entire sample, DTP had a low-to-moderate discrimination ability (AUC 0.698 ± 0.024). A DTP ≥2 h has a low sensitivity for coagulase-negative staphylococci (60%) and very low for S. aureus (34%), enterococci (40%) and non-AmpC-producing Enterobacteriaceae (42%). A DTP cut-off of 1 h improved sensitivity (90%) for AmpC-producing Enterobacteriaceae. CONCLUSIONS: Differential time to positivity performs well for diagnosing CRBSI only when AmpC-producing Enterobacteriaceae and P. aeruginosa are involved. Performance is low for common Gram-positive organisms and non-AmpC-producing enteric bacilli; a negative test should not be used to rule out CRBSI due to these microorganisms. A DTP ≥1 h may improve accuracy for AmpC-producing Enterobacteriaceae, particularly Enterobacter spp.

Comparison of semiquantitative and differential time to positivity methods for the diagnosis of central line-associated bloodstream infections in an intensive care unit.

INTRODUCTION: Central line-associated bloodstream infections (CLABSIs) adversely affect patients' hospitalization. AIM: We compared semiquantitative roll plate (SQRP) and differential time to positivity (DTP) culture methods in diagnosing CLABSIs. METHODOLOGY: A retrospective study was conducted in an intensive care unit (ICU) from January 2013 to August 2014. All ICU patients with suspected CLABSIs were included. Blood cultures were taken, while central venous catheter (CVC) tips were cultured using the roll-tip method. DTP was considered positive if CVC lumen blood cultures became positive at least 2 h prior to concurrently drawn peripheral blood cultures with an identical micro-organism. SQRP method was considered positive when ≥15 c.f.u. of a micro-organism identical to that of blood cultures grew. Measures of diagnostic accuracy were calculated. RESULTS: SQRP displayed high sensitivity (94.7 %), while DTP showed high specificity (82.5 %). SQRP combined with DTP displayed 100  % sensitivity and negative predictive value. CONCLUSION: SQRP and DTP methods should be evaluated in combination.

Differential time to positivity of central and peripheral blood cultures is inaccurate for the diagnosis of Staphylococcus aureus long-term catheter-related sepsis.

OBJECTIVES: Differential time to positivity of cultures of blood drawn simultaneously from central venous catheter and peripheral sites is widely used to diagnose catheter-related bloodstream infections without removing the catheter. However, the accuracy of this technique for some pathogens, such as Staphylococcus aureus, is debated in routine practice. METHODS: In a 320-bed reference cancer centre, the charts of patients with at least one blood culture positive for S. aureus among paired blood cultures drawn over a six-year period were studied retrospectively. Microbiological data were extracted from the prospectively compiled database of the microbiology unit. Data concerning the 149 patients included were reviewed retrospectively by independent physicians blinded to the absolute and differential times to positivity, in order to establish or refute the diagnosis of catheter-related sepsis. Due to missing data, 48 charts were excluded, so 101 cases were actually analysed. The diagnosis was established in 62 cases, refuted in 15 cases and inconclusive in the remaining 24 cases. RESULTS: For the 64 patients with both central and peripheral positive blood cultures, the differential positivity time was significantly greater for patients with catheter-related bloodstream infections due to S. aureus (P<0.02). However, because of the high number of false-negative cases, the classic cut-off limit of 120 min showed 100% specificity but only 42% sensitivity for the diagnosis of catheter-related bloodstream infection due to S. aureus. CONCLUSIONS: These results strongly suggest that despite its high specificity, the differential time to positivity may not be reliable to rule out catheter-related bloodstream infection due to S. aureus.

Diferença de tempo de positividade: método útil no diagnóstico de infecção de corrente sanguínea relacionada com cateter? / Differential time to positivity: a useful tool for the diagnosis of catheter-related infections?

INTRODUÇÃO: As infecções de corrente sanguínea relacionadas com cateter (ICSRCs) apresentam impacto significativo na morbidade e na mortalidade de pacientes internados, além de elevar custos hospitalares. A utilização de equipamentos automatizados no processamento de hemoculturas gerou uma alternativa para diagnóstico de ICSRC por meio da análise da diferença de tempo de positividade (DTP) entre hemoculturas pareadas (coletadas simultaneamente) de sangue periférico e sangue de cateter. Um diagnóstico acurado e rápido dessas infecções pode otimizar as condutas clínicas e terapêuticas, poupando a retirada precoce dos cateteres. OBJETIVOS: Avaliar na rotina a DTP como ferramenta auxiliar no diagnóstico de ICSRC e determinar os principais microrganismos isolados. MÉTODOS: Foram avaliadas retrospectivamente hemoculturas coletadas no complexo do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HC/FMUSP) de maio a agosto de 2008. Somente amostras que apresentaram DTP maior que 120 minutos foram consideradas possíveis ICSRCs pelo critério laboratorial. RESULTADOS: A seção processou 11.017 hemoculturas aeróbias durante o período de estudo; somente 5% foram coletadas de forma pareada. Destas, 148 (28%) foram positivas, sendo 9% com crescimento somente em sangue periférico, 41% somente em sangue de cateter e 50% em ambas as amostras com 88% de homologia de microrganismos identificados. A DTP apresentou valores acima de 120 minutos em 50% dos casos e os microrganismos mais isolados foram Staphylococcus aureus (22%), Candida spp. (18%), Klebsiella spp. (7%) e Enterobacter spp. (7%). CONCLUSÃO: A determinação da DTP como ferramenta auxiliar no diagnóstico de ICSRC é viável e fácil de ser executada em laboratórios de rotina com automação, porém o processo de coleta das amostras pareadas deve ser rigidamente padronizado.

INTRODUCTION: Not only do catheter related bloodstream infections (CRBSIs) have considerable impact on morbidity and mortality in hospitalized patients, but they also raise hospital costs. The use of automated equipment in blood culture processing has allowed an alternative diagnosis of CRBSI by analyzing the differential time to positivity (DTP) of paired blood cultures (collected simultaneously) of peripheral blood and catheter blood. A rapid and accurate diagnosis of these infections may optimize clinical and therapeutic management, which prevents early catheter removal. OBJECTIVES: To assess DTP as an auxiliary tool for the diagnosis of CRBSI as well as to determine the main isolated microorganisms. METHODS: We evaluated blood cultures that had previously been collected in the complex Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HC/FMUSP) from May to August 2008. According to the laboratory criteria, only DTP higher than 120 minutes was regarded as possible CRBSI. RESULTS: During the investigation period 11,017 aerobic blood cultures were processed, from which only 5% were paired samples. One hundred forty-eight (28%) samples were positive, from which 9% showed growth in peripheral blood, 41% only in catheter blood and 50% in both blood samples with 88% homology of identified microorganisms. DTP higher than 120 minutes occurred in 50% of the cases. The most common isolated microorganisms were: Staphylococcus aureus (22%), Candida spp. (18%), Klebsiella spp (7%). and Enterobacter spp (7%). CONCLUSION: The determination of the DTP as an auxiliary tool for the diagnosis of CRBSI is feasible and easily performed in clinical laboratories with automation, although the process of paired sample collection must be rigidly standardized.