Search

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.

Background Of all microbiological tests performed, blood cultures have the most impact on patient care. Timely results are essential, especially in the management of sepsis. While there are multiple available blood culture systems on the market, they have never been compared in a prospective study in a critically ill population. Methods We performed an analysis of the FABLED study cohort to compare culture results and time to positivity (TTP) of 2 widely used blood culture systems: BacT/Alert and BACTEC. In this multisite prospective study, patients with severe manifestations of sepsis had cultures drawn before antibiotics using systematic enrollment criteria and blood drawing methodology allowing for minimization of pre-analytical biases. Results We enrolled 315 patients; 144 had blood cultures (47 positive) with BacT/Alert and 171 with BACTEC (53 positive). Patients whose blood cultures were processed using the BacT/Alert system were younger (median, 64 vs 70 years; P = .003), had a higher proportion of HIV (9.03% vs 1.75%; P = .008) and a lower qSOFA (P = .003). There were no statistically significant differences in the most commonly identified bacterial species. TTP was shorter for BACTEC (median [interquartile range {IQR}], 12.5 [10–14] hours) compared with BacT/Alert (median [IQR], 17 [14–21] hours; P Conclusions In this large prospective multi-centre study comparing the two blood culture systems among patients with severe manifestations of sepsis, and using a rigorous pre-analytical methodology, the BACTEC system yielded positive culture results 4.5 hours earlier than BacT/Alert. These results apply to commonly isolated bacteria. However, our study design did not allow direct comparison of TTP for unusual pathogens nor of clinical sensitivity between systems. More research is needed to determine the clinical implications of this finding.

This work was supported by the Swedish Research Council (grant 521-2011-3442 to R. J. S. and U. S. H. S.), the Innovative Medicines Initiative Joint Undertaking (award 115337, with contribution from the European Union’s Seventh Framework Programme [FP7/2007–2013] and the European Federation of Pharmaceutical Industries and Associations [in-kind contribution]), the European and Developing Countries Clinical Trials Partnership (awards IP.2007.32011.011, IP.2007.32011.012, and IP.2007.32011.013), the Netherlands-African Partnership for Capacity Development and Clinical Interventions Against Poverty-Related Diseases, and the Bill and Melinda Gates Foundation. Background The currently recommended rifampicin dose (10 mg/kg) for treating tuberculosis is suboptimal. The PanACEA HIGHRIF1 trial evaluated the pharmacokinetics and early bactericidal activity of rifampicin doses of up to 40 mg/kg. Conventional statistical analyses revealed no significant exposure-response relationship. Our objectives were to explore the exposure-response relationship for high-dose rifampicin by using pharmacokinetic-pharmacodynamic modeling and to predict the early bactericidal activity of 50 mg/kg rifampicin. Methods Data included time to Mycobacterium tuberculosis positivity of liquid cultures of sputum specimens from 83 patients with tuberculosis who were treated with 10 mg/kg rifampicin (n = 8; reference arm) or 20, 25, 30, 35, or 40 mg/kg rifampicin (n = 15/arm) for 7 days. We used a semimechanistic time-to-event approach to model the time-to-positivity data. Rifampicin exposure and baseline time to culture positivity were explored as covariates. Results The baseline time to culture positivity was a significant covariate on the predicted initial bacterial load, and rifampicin exposure was a significant covariate on the bacterial kill rate in sputum resulting in increased early bactericidal activity. The 90% prediction interval for the predicted median day 7 increase in time to positivity for 50 mg/kg rifampicin was 7.25–10.3 days. Conclusions A significant exposure-response relationship was found between rifampicin exposure and early bactericidal activity. Clinical trial simulations showed greater early bactericidal activity for 50 mg/kg rifampicin. Postprint

Many bloodstream infections (BSI) in patients with central venous catheters (CVC) are not catheter-related (CR). Assessment of catheter involvement without catheter withdrawal has not been studied in candidemia. We assessed the value of conservative techniques to evaluate catheters as the origin of candidemia in patients with CVC in a prospective cohort study (superficial Gram stain and culture, Kite technique (Gram stain and culture of the first 1 cm blood drawn from the CVC), proportion of positive blood cultures (PPBCs), differential time to positivity (DTP), and minimal time to positivity (MTP)). All catheters were cultured at withdrawal. From June 2008 to January 2012, 22 cases fulfilled the inclusion criteria. CR-candidemia (CRC) was confirmed in 10. Validity values for predicting CRC were: superficial Gram stain (S, 30%; Sp, 81.83%; PPV, 60%; NPV, 56.3%; Ac, 57.1%), superficial cultures (S, 40%; Sp, 75%; PPV, 57.1%; NPV, 60%; Ac, 59.1%), Kite Gram stain (S, 33.3%; Sp, 66.7%; PPV, 50%; NPV, 50%; Ac, 50%), Kite culture (S, 80%; Sp, 66.7%; PPV, 66.7%; NPV, 80%; Ac, 72.7%), PPBC (S, 50%; Sp, 41.7%; PPV, 41.7%; NPV, 50.0%; Ac, 45.5%), DTP (S, 100%; Sp, 33.3%; PPV, 55.6%; NPV, 100%; Ac, 63.6%), and MTTP (S, 70%; Sp, 58.3%; PPV, 58.3%; NPV, 70%; Ac, 63.6%). While combinations of two tests improved sensitivity and NPV, more than two tests did not improve validity values. Classic tests to assess CR-BSI caused by bacteria cannot be reliably used to diagnose CRC. Combinations of tests could be useful, but more and larger studies are required.

Objective: To develop a novel clinical diagnostic method to distinguish bacteremia from blood contamination due to coagulase-negative staphylococci (CNS) by using the ratio of the time to positivity (TTP) of a blood culture with positive results to its serum procalcitonin (PCT) level. Methods: We retrospectively reviewed the clinical and microbiological records of 102 patients who had 1 or more blood cultures that tested positive for CNS from August 2007 through February 2012. Results: Receiver operating characteristic (ROC) curve analysis indicated that, at a cutoff of 1.24 ng per mL, 21.5 hours, and 22.5 (hours × mL)/ng,the TTP to PCT ratio, PCT level, and TTP yielded the most favorable discrimination for bacteremia caused by CNS, with sensitivities of 85.7%, 78.6%, and 61.9%,respectively, and specificities of 80.0%, 78.3%, and 61.7%,respectively. The TTP to PCT ratio was the most accurate of the studied variables in predicting CNS-triggered bacteremia levels. Conclusion: The TTP to PCT ratio is a useful predictor to differentiate the culture samples that test positive, revealing the presence of CNS bacteremia, from those that are merely contaminated.

Background The decision of catheter removal in neutropenic patients with candidemia is difficult because they usually have surgically implanted catheter, and CRC are less frequent than in non-neutropenic patients. However, there are limited data on distinguishing CRC from non-CRC before catheter removal. We thus evaluated the diagnostic performances of DTP to diagnose CRC in neutropenic cancer patients with suspected CRC. Methods All adult neutropenic cancer patients with candidemia were enrolled in a tertiary care hospital from July 2012 to December 2016. Definite CRC was defined if ≥15 CFU of Candida spp. in a removed catheter tip. Probable CRC was defined if (1) one to 14 CFU in catheter tip, and clinical improvement within 48 hours after catheter removal with antifungal agent therapy or (2) the infection was refractory to antifungal therapy alone but improved within 48 hours after catheter removal. Non-CRC was defined if any of the following conditions were satisfied: (1) catheter tip cultures were negative and a noncatheter source of candidemia was found by culture, (2) the catheter tip cultures within 24 h before the start of antifungal therapy were negative, or (3) the clinical improvement before or without catheter removal. If the above conditions are not met, they were grouped into indeterminate, and were excluded from the final analysis. We defined the DTP as the difference in the time to positivity between blood cultures drawn simultaneously from the central vein and a peripheral vein. Results A total of 35 neutropenic patients with candidemia were enrolled. Of these, 15 patients (43%) with CRC (6 definite and nine probable) and 17 (48.5%) with non-CRC were finally analyzed, excluding threeindeterminate candidemia. On the basis of the receiver operating characteristics (ROC) curve, the optimal cut-off was ≥1.45 hours and the area under the ROC curve was 0.89 (95% CI, 76 to 100) in diagnosing CRC. Of the 15 patients with CRC, 11 (73%) revealed positive DTP, whereas none of the 17 patients with non-CRC exhibits positive DTP. The sensitivity and specificity of DTP for the diagnosis of CRC were 73% (95% CI, 58 to 94) and 100% (95% CI, 71 to 100), respectively. Conclusion DTP appears to be useful to rule in CRC and DTP ≥ 1.45 hours to be the optimal cut-off for CRC in neutropenic cancer patients. Disclosures All authors: No reported disclosures.

Catheter-related bloodstream infections (CRBIs) are a common problem in paediatrics. Sterile insertion and proper care of the catheter is likely more important than the type of catheter in determining the rate of CRBIs. The accuracy of the diagnosis of CRBIs can be improved by comparing the time to positivity or the concentration of organisms in blood drawn through the catheter with blood drawn from other sites, or by changing the catheter over a guidewire and culturing the removed catheter. When a CRBI is suspected, the catheter should be removed if it is no longer required, the child is hemodynamically unstable, there are metastatic foci of infection, the infecting organism is Candida or a mycobacterium, or there is a tunnel infection. The necessity for catheter removal is controversial if the infecting organism is Staphylococcus aureus or a Gram-negative organism. In most other situations, the catheter only needs to be removed if bacteremia persists despite appropriate antibiotic use.