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Non-β-hemolytic streptococci (NBHS) cause infective endocarditis (IE) and a short blood culture time to positivity (TTP) is associated with risk of IE in bacteremia with other pathogens. In this retrospective population-based cohort study, we investigate if TTP is associated to IE or mortality. Of 263 episodes with NBHS bacteremia, 28 represented IE and the median TTP did not differ significantly between episodes with IE (15 h) and non-IE (15 h) (p=0.51). TTP was similar among those who survived and those who died within 30 days. However, TTP significantly differed when comparing the different streptococcal groups (p

Background Few mortality-scoring models are available for solid tumor patients who are predisposed to develop Escherichia coli–caused bloodstream infection (ECBSI). We aimed to develop a mortality-scoring model by using information from blood culture time to positivity (TTP) and other clinical variables. Methods A cohort of solid tumor patients who were admitted to hospital with ECBSI and received empirical antimicrobial therapy was enrolled. Survivors and non-survivors were compared to identify the risk factors of in-hospital mortality. Univariable and multivariable regression analyses were adopted to identify the mortality-associated predictors. Risk scores were assigned by weighting the regression coefficients with corresponding natural logarithm of the odds ratio for each predictor. Results Solid tumor patients with ECBSI were distributed in the development and validation groups, respectively. Six mortality-associated predictors were identified and included in the scoring model: acute respiratory distress (ARDS), TTP ≤ 8 h, inappropriate antibiotic therapy, blood transfusion, fever ≥ 39 °C, and metastasis. Prognostic scores were categorized into three groups that predicted mortality: low risk ( 20% mortality, ≥ 3 points). The TTP-incorporated scoring model showed excellent discrimination and calibration for both groups, with AUC being 0.833 vs 0.844, respectively, and no significant difference in the Hosmer–Lemeshow test (6.709, P = 0.48) and the chi-square test (6.993, P = 0.46). Youden index showed the best cutoff value of ≥ 3 with 76.11% sensitivity and 79.29% specificity. TTP-incorporated scoring model had higher AUC than no TTP-incorporated model (0.837 vs 0.817, P Conclusions Our TTP-incorporated scoring model was associated with improving capability in predicting ECBSI-related mortality. It can be a practical tool for clinicians to identify and manage bacteremic solid tumor patients with high risk of mortality.

Patients with viral respiratory infections often present symptoms compatible with bloodstream infections. Consequently, the winter period commonly associated with epidemic respiratory illnesses shows an increase in the number of blood cultures (BC) and to occasional saturation of automated BC systems. Here, we explored the seasonal variations in BC samples and the potential impact of shortening the incubation time of BC when automated BC systems are close to saturation. A retrospective study was conducted during a 3-year period in 4 hospitals located in the Paris region, France. All aerobic and anaerobic bottles were included, except pediatric bottles and those sampled for suspicion of endocarditis. The number of BC bottles collected during the winter period was compared to the annual baseline. All bottles positive after a 4-day incubation were analyzed regarding clinical and microbiological findings. The number of BC bottles was significantly higher during the winter periods, compared to the annual baseline (up to 14%). A total of 292,349 BC bottles were analyzed with 23,363 (8.0%) positive, including 236 (1%) after a 4-day incubation. Of these 236 bottles, 76 (64.8%) were positive with a contaminant, 78 (33.1%) with a clinically significant microorganism identified for the same patient in the previous 4 days, and only 5 (2.1%) with a clinically significant microorganism not previously identified. Winter periods were associated with a significant increase in BC samples. Shortening the incubation time of BC bottles from 5 to 4 days seems a relevant option when automated BC systems are close to saturation. Supplementary Information The online version contains supplementary material available at 10.1007/s10096-021-04248-9.

Recommendations by manufacturers depict that blood culture bottles are to be loaded into the automated machines as soon as possible after the blood collection. But it has been noticed that in peripheral set-ups where round the clock laboratory facility is not available or which are located far from the reference labs, or even in the tertiary care centres, delay occurs prior to the bottle loading into the instruments. In our study, we have compared the effect of pre-incubating the blood culture bottles at various temperatures like 4°C, room temperature and 37°C for various holding times, such as 2, 6, 12 and 24 hours simulating the delay in transport time in BACTEC plus Aerobic and BACTALERT FA plus systems in a tertiary care set up. We included five recent clinical isolates of different microorganisms in our study, such as Staphylococcus aurous, Streptococcus, Escherichia coli, Pseudomonas aeruginosa and Candida albicans. Standard inoculum was prepared for each organism and 3 ml of it was added with 10 ml of citrated human blood and then inoculated into blood culture vial (BACTALERT FA plus and BACTEC Plus). Organism recovery rate, time to detection and rates of false-negativity from both the instruments were evaluated by using seeded blood culture vial and controls with delayed entry. Performance wise analysis showed that the overall isolation rate of the organisms from BACTEC bottles was higher compared to BACTALERT. Also BACTEC showed less average TTD compared to BACTALERT for Pseudomonas aeruginosa, Streptococcus and candida albicans but for E. coli and S. aureus BACTALERT showed earlier detection. To conclude, storage of the inoculated bottles at room temperature gave optimal recovery of the organisms for both BACTEC and BACTALERT systems, if delayed entry is inevitable. Keyword: Delayed vial entry effect on recovery of microorganisms.

The time to positivity (TTP) of blood culture has significant value for clinicians. However, almost all subjects of previous studies regarding TTP were adults and early infants. Therefore, careful attention is required when referring to previously published data, which might differ according to the age of subjects, as the tendency of infectious focus and pathogens identified from culture vary with age. In this study, we compared the TTP between two pediatric age groups (≤12 months and 13 months to 15 years [12 months]) at a teaching hospital during a 5-year period. Of the 95 subjects, 41 and 54 were aged ≤12 and 12 months, among whom true pathogenic bacteria were identified in 12 (29.3%) and 19 (35.2%), respectively. The median TTP for the younger group with pathogenic bacteria was 11.2 (interquartile range, 10.0-11.9) hours, which was significantly shorter than that for the older group (12.6 [interquartile range, 11.9-16.9] hours) (P = 0.01). At 12 h after the initiation of culture, the younger group with pathogenic bacteria had a significantly higher positivity rate (83.3%) than the older group (26.3%) (P 0.01). The times required for the positivity to exceed 90% were 13.4 and 20.1 h for the younger and older pathogenic groups and 30.4 and 67.8 h for the younger and older contaminant groups, respectively. The range of TTP could be assessed more accurately by considering the effect of age on the infectious background.

Aim: To determine the appropriateness of blood volume in automated blood culture bottles of the BACT/ALERT 3D system, its effect on isolation rate and time to positivity of pathogens. Materials and Methods: The study was carried out in a tertiary care hospital in South India from 1st March 2018 to 31st August 2018. Automated blood culture bottles sent to Microbiology laboratory for blood culture were included in the study. The bottles were weighted by electronic weighing balance. The filled blood culture bottles received at microbiology laboratory were re-weighed and was categorized into appropriately filled and inappropriately filled bottles. Frequency of appropriately filled bottles and inappropriately filled bottles was expressed in percentage. Result: A total of 8740 blood culture bottles were included in the study, out of which the blood volume was found to be suboptimum in 3978 bottles (45.5%), optimum in 3498 bottles (40%) and overfilled in 1264 bottles (14.5%). There was an increase in the number of blood culture bottles with optimum blood volume from 35.1% in March to 58.12% in August. The average TTP for true pathogens was found to be 16.72 hrs. with optimum blood volume, 17 hrs. with overfilled blood volume and 21.5 hrs. with sub-optimum blood volume. The isolation rate for true pathogens was found to be 88.62% with optimum blood volume, 86.43% with overfilled blood volume and 70.01% with sub-optimum. The false positive rate was found to be 4.1% with overfilled blood volume, 1.6%with sub-optimum and 1.4%with optimum blood volume. Conclusion: Through this study, the correlation between the blood volume with the isolation rate, time to positivity and false positivity of blood culture isolates was established. Keywords: Blood culture, Blood volume, BACT/ALERT 3D, Time to positivity, Isolation rate.

Background : The comparison of the performance of FAPlus/FNPlus bottles and combination of SA/SN and FA/FN bottles is not yet reported. Methods : We used human blood samples to investigate microorganism detection rates and the time to positivity (TTP) in a before-vs.-after study (a combination of SA/SN and FA/FN bottles from September 2012 to August 2013 vs. FAPlus/FNPlus bottles from September 2013 to August 2014). Results : The microorganism detection rate was significantly higher in the later period than in the earlier period (11.2% vs. 9.6%, P 0.001), particularly for Enterococcus and Streptococcus species, nonfermentative Gram-negative bacilli, and Helicobacter cinaedi. TTP for pathogens was longer when FAPlus/FNPlus bottles were used than when a combination of SA/SN and FA/FN bottles was used (14.9 vs. 13.3 h, P = 0.014), particularly, in the case of Gram-negative bacilli including Escherichia coli. Conclusion : The microorganism detection rate was improved with the use of FAPlus/FNPlus bottles compared with the combination of SA/SN and FA/FN bottles ; however, FAPlus/FNPlus bottles seemed to be inferior to SA/SN and FA/FN bottles in terms of TTP. J. Med. Invest. 67 : 90-94, February, 2020.

Background: In many infants, treatment is started for suspicion of early onset sepsis (EOS), of whom the majority do not have an infection. Early prediction of the absence of a culture-proven sepsis (CPS) would significantly reduce the time of antibiotic treatment and hospitalization. Our objective was to analyze 3 criteria in infants with CPS: positive blood culture (BC) at 24 hours after the onset of suspicion of EOS (OSEOS), C-reactive protein (CRP) >= 10 mg/L and clinical signs of infection, so we can consequently consider to stop antibiotic treatment in infants without these criteria.Methods: We included all infants with suspicion of EOS from 2007 until 2020. The proportion was calculated of (1) infants with CPS with, at 24 hours, a positive BC and/or CRP >= 10 mg/L and/or clinical signs of infection and (2) infants without CPS with CRP = 24 hours in 8 (16%) infants, of whom 7 infants had a raised CRP and/or clinical symptoms of infection within 24 hours. In 1095 (74%) of infants without CPS in whom CRP was measured between 12 and 24 hours after OSEOS, CRP was

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Objectives: Concern for late detection of bacterial pathogens is a barrier to early de-escalation efforts. The purpose of this study was to assess blood, respiratory and urine culture results at 72 h to test the hypothesis that early negative culture results have a clinically meaningful negative predictive value. Methods: We retrospectively reviewed all patients admitted to the medical intensive care unit between March 2012 and July 2018 with blood cultures obtained. Blood, respiratory and urine culture results were assessed for time to positivity, defined as the time between culture collection and preliminary species identification. The primary outcome was the negative predictive value of negative blood culture results at 72 h. Secondary outcomes included sensitivity, specificity, positive predictive value and negative predictive value of blood, respiratory and urine culture results. Results: The analysis included 1567 blood, 514 respiratory and 1059 urine cultures. Of the blood, respiratory and urine cultures ultimately positive, 90.3%, 76.2% and 90.4% were positive at 72 h. The negative predictive value of negative 72-h blood, respiratory and urine cultures were 0.99, 0.82 and 0.97, respectively. Antibiotic de-escalation had good specificity, positive predictive value and negative predictive value for finalized negative cultures. Conclusion: Negative blood and urine culture results at 72 h had a high negative predictive value. These findings have important ramifications for antimicrobial stewardship efforts and support protocolized re-evaluation of empiric antibiotic therapy at 72 h. Caution should be used in patients with clinically suspected pneumonia, since negative respiratory culture results at 72 h were weakly predictive of finalized negative cultures.

The emergence of carbapenem-resistant Enterobacterales (CRE) is a matter of public health concern. Carbapenemases are the main mechanism of resistance among CRE, and its rapid detection is essential. The detection of carbapenemases usually requires culture-based methods and molecular assays, which may be costly and need long turnaround times. Recently, an easy and rapid immunochromatographic assay for carbapenemases (OXA-48, KPC, and NDM) detection based in lateral flow immunoassay with specific monoclonal antibodies on a nitrocellulose membrane has been developed. We aimed to evaluate the RESIST-3 O.K.N. in colonies from pure culture as well as in spiked blood cultures with Enterobacterales. All carbapenemase producers (CP) presenting the OXA-48-like, KPC, and NDM enzymes presented positive results in both pure colonies and spiked blood cultures. None of the carbapenemase non-producers (CNP) presented positive results in the tests. A total of 97% CP isolates presented positive results in pure colonies in less than 5 min. For CP directly from blood culture, the mean time to positivity for OXA-48-like and KPC was 1 min, whereas it was 25 min for NDM. Our results indicate that this immunoassay can be used to detect carbapenemases directly from blood culture bottles in a routine diagnostic laboratory, which would reduce the turnaround time of CP detection.

IntroductionBacteremia causes a high mortality rate. Detection of bacteremia is needed as quickly as possible. The gold standard for bacteremia is blood culture which takes between 24-48 hours. Procalcitonin (PCT) is a marker of infection that is caused by bacteria that can be detected quickly in 2-6 hours. Time to positivity (TTP) blood culture is affected by the initial amount of bacteria and the addition of procalcitonin stimulated by bacteria that causes bacteremia where short TTP and high PCT show bad clinical conditions. Materials and MethodsAnalitical cross sectional research on patients with bacteremia. Fourty six bacteremia cases become the sample of research. Time to Positivity is calculated with Bactec 9050 and Procalcitonin is analyzed with mini VIDAS B.R.A.H.M.S. Examination is conducted in Department of Clinical Pathology FK-USU/ Installation of Clinical Pathology of RSUP H. Adam Malik, Medan, June – October 2016. ResultsThere was significant correlation between Time to Positivity blood culture and procalcitonin on bacteremia patients (p0.05). Procalcitonin was significantly higher on bacteremia which was caused by gram-negative bacteria compared to gram-positive bacteria (p

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.

Significant reductions in catheter-related bloodstream infections (CRBSI) have occurred in the United States. Reductions in CRBSIs are attributed to the widespread implementation of the practice-based measures and innovations in the diagnosis, treatment, and prevention of CRBSI. Diagnosis of CRBSI historically required removal of the central venous catheter (CVC) for catheter tip culture. Removing the CVC for CRBSI diagnosis predisposes many patients to potential life-threatening complications. Advances in diagnostic techniques such as culturing catheter hubs, catheter entry site cultures, applying differential time to positivity, molecular diagnostics, biomarkers, and innovative approaches like biosensors on the CVC lumen may provide an alternative to CVC removal. Removal of the CVC is common for the treatment of CRBSI; however, antimicrobial lock therapy is increasingly used as a CVC salvage method. Implementation of newer technology such as antimicrobial coated catheters, chlorhexidine-impregnated dressings, and antiseptic port protectors are crucial for the prevention of CRBSIs. Increasing evidence also support newer sutureless CVC securement devices prevent CRBSIs. CRBSI remains a significant clinical problem despite advances made in the diagnosis, management, and prevention. Molecular techniques are increasingly being used for pathogen identification in CRBSI, but the optimal diagnostic test remains debatable. Increasing experience is being gained with antimicrobial lock therapy for CRBSI treatment with catheter salvage. Use and adherence to practice-based measures and technological innovations has significantly reduced CRBSIs. Continued efforts are required to develop a cost-effective and targeted approach for CRBSI prevention.

We aimed to investigate the relationship between time to positivity (TTP) of blood cultures and clinical outcomes in children with S. pneumoniae bacteremia. Children with S. pneumoniae bacteremia hospitalized in Children’s Hospital of Chongqing Medical University from May 2011 to December 2017 were enrolled retrospectively. Overall, 136 children with S. pneumoniae bacteremia were enrolled. The standard cutoff TTP was 12 h. We stated that in-hospital mortality is significantly higher in the early TTP (≤ 12 h) group than that in the late TTP (> 12 h) group (41.70% vs 8.00%, P

Objective Artificial sputum spiked with Mycobacterium tuberculosis could serve for validation of procedures that determine viable mycobacterial load. Design Artificial sputum specimens prepared in-house were spiked with low, medium or high concentrations of Mycobacterium tuberculosis H37Rv stock solution. In a first series, a single technologist processed two batches of specimens daily with high load that were stored refrigerated or at room temperature for up to 8 days. In a second series, nine different technologists processed freshly made batches of specimens with low, medium or high loads. We recorded time to positivity (TTP) in duplicate liquid cultures made from each specimen. Results Specimens were well grouped around the mean TTP (hours; standard deviation) of low: 271.7 (25.9), medium: 233.5 (16.3), and two batches of high load: 186.9 (12.3) and 191.8 (9.0), respectively. A variance component model that included load, storage temperature, days of storage until processing, batch of specimens made, sample ID and technologist ID as random effects in a linear mixed-effects model identified only load, technologist and residual as significant contributors to overall TTP variance. Conclusion Artificial sputum specimens with reproducible and stable viable mycobacterial loads can be made that could serve for training and validation purposes.

Background In resource-limited settings, sputum smear conversion is used to document treatment response. Many People living with HIV (PLHIV) are smear-negative at baseline. The Xpert MTB/RIF test can indirectly measure bacterial load through cycle threshold (ct) values. This study aimed to determine if baseline Xpert MTB/RIF could predict time to culture negativity in PLHIV with newly diagnosed TB. Methods A subset of 138 PLHIV from the ‘SOUTH’ study on outcomes related to TB and antiretroviral drug concentrations were included. Bacterial load was estimated by Mycobacterium Growth Indicator Tubes (MGIT) culture time-to-positivity (TTP) and Lowenstein Jensen (LJ) colony counts. Changes in TTP and colony counts were analyzed with Poisson Generalised Estimating Equations (GEE) and multilevel ordered logistic regression models, respectively, while time to culture negativity analysed with Cox proportional hazard models. ROC curves were used to explore the accuracy of the ct value in predicting culture negativity. Results A total of 81 patients (58.7%) were males, median age 34 (IQR 29 ̶ 40) years, median CD4 cell count of 180 (IQR 68 ̶ 345) cells/μL and 77.5% were ART naive. The median baseline ct value was 25.1 (IQR 21.0 ̶ 30.1). A unit Increase in the ct value was associated with a 5% (IRR = 1.05 95% CI 1.04 ̶ 1.06) and 3% (IRR = 1.03 95% CI 1.03 ̶ 1.04) increase in TTP at week 2 and 4 respectively. With LJ culture, a patient’s colony grade was reduced by 0.86 times (0R = 0.86 95% CI 0.74 ̶ 0.97) at week 2 and 0.84 times (OR = 0.84 95% CI 0.79 ̶ 0.95 P = 0.002) at week 4 for every unit increase in the baseline ct value. There was a 3% higher likelihood of earlier conversion to negativity for every unit increase in the ct value. A ct cut point ≥28 best predicted culture negativity at week 4 with a sensitivity of 91. 7% & specificity 53.7% while a cut point ≥23 best predicted culture negativity at week 8. Conclusion Baseline Xpert MTB/RIF ct values predict sputum conversion in PLHIV on anti-TB treatment. Surrogate biomarkers for sputum conversion in PLHIV are still a research priority.

BackgroundBlood cultures are one of the most important tests performed by microbiology laboratories. Many hospitals, particularly in low and middle-income countries, lack either microbiology services or staff to provide 24 h services resulting in delays to blood culture incubation. There is insufficient guidance on how to transport/store blood cultures if delays before incubation are unavoidable, particularly if ambient temperatures are high. This study set out to address this knowledge gap.MethodsIn three South East Asian countries, four different blood culture systems (two manual and two automated) were used to test blood cultures spiked with five common bacterial pathogens. Prior to incubation the spiked blood culture bottles were stored at different temperatures (25 °C, in a cool-box at ambient temperature, or at 40 °C) for different lengths of time (0 h, 6 h, 12 h or 24 h). The impacts of these different storage conditions on positive blood culture yield and on time to positivity were examined.ResultsThere was no significant loss in yield when blood cultures were stored ConclusionBlood cultures should be incubated with minimal delay to maximize pathogen recovery and timely result reporting, however, this study provides some reassurance that unavoidable delays can be managed to minimize negative impacts. If delays to incubation ≥ 12 h are unavoidable, transportation at a temperature not exceeding 25 °C, and blind sub-cultures prior to incubation should be considered.

Timely diagnosis of microorganisms in blood cultures is necessary to optimize therapy. Although blood culture media and systems have evolved for decades, the standard interval for incubation prior to being discarded as negative has remained 5 days. Here, we evaluated the optimal incubation time for the BacT/Alert Virtuo blood culture detection system (bioMérieux) using FA Plus (aerobic) and FN Plus (anaerobic) resin culture bottles in routine clinical use., Timely diagnosis of microorganisms in blood cultures is necessary to optimize therapy. Although blood culture media and systems have evolved for decades, the standard interval for incubation prior to being discarded as negative has remained 5 days. Here, we evaluated the optimal incubation time for the BacT/Alert Virtuo blood culture detection system (bioMérieux) using FA Plus (aerobic) and FN Plus (anaerobic) resin culture bottles in routine clinical use. Following institutional review board (IRB) approval, a retrospective review evaluated the outcomes of 158,710 bottles collected between November 2018 and October 2019. The number of positive blood bottles was 13,592 (8.6%); 99% of positive aerobic and anaerobic bottles flagged positive by 91.5 and 108 h, respectively. The mean (median) times to positivity were 18.4 h (15.6 h) for Staphylococcus aureus, 12.3 h (9.5 h) for Escherichia coli, 22.2 h (15.9 h) for Pseudomonas aeruginosa, and 48.9 h (42.9 h) for Candida spp. Only 175 bottles (0.1% of all bottles) flagged positive after 4 days of incubation; 89 (51%) of these bottles grew Cutibacterium (Propionibacterium) species. Chart review of blood cultures positive after 4 days (96 h) rarely had a clinical impact and sometimes had a negative impact on patient care. Finally, a seeded study of the HACEK group (i.e., Haemophilus, Aggregatibacter, Cardiobacterium, Eikenella, and Kingella), historically associated with delayed blood culture positivity, demonstrated no benefit to extended incubation beyond 4 days. Collectively, these findings demonstrated that a 4-day incubation time was sufficient for the Virtuo system and media. Implementation of the 4-day incubation time could enhance clinically relevant results by reducing recovery of contaminants and finalizing blood cultures 1 day earlier.

Time to blood culture positivity (TTP) is an indirect measure of bacterial concentration in blood. A short TTP has been linked to the presence of infective endocarditis (IE) and to poor prognosis in Staphylococcus aureus bacteremia. We analyze factors influencing TTP in bacteremia with Enterococcus faecalis. This retrospective observational study of medical records included adults diagnosed with monomicrobial E. faecalis bacteremia between 2015 and 2018 in the Skåne region (Sweden). For each episode, the shortest TTP was recorded. Median TTP was compared between patients grouped based on age, sex, comorbidity, site of acquisition, and focus of infection. Using a dichotomized TTP (shorter or longer than 12 h), a multivariable logistic regression for factors associated to TTP was performed. The association between TTP and IE or mortality was evaluated. Three hundred sixty-seven episodes with monomicrobial E. faecalis bacteremia with the corresponding TTP were identified. Median TTP for the entire cohort was 11.6 (IQR 9.9–14.1) h and a significantly shorter TTP was noted for episodes which represented IE (n = 55, 9.4 (IQR 6.4–10.6) h). Only IE remained associated with a short TTP (≤ 12 h) in binary logistic regression analysis. Factors associated with IE were investigated and TTP was associated with IE also when adjusted for age, gender, comorbidity, and nosocomial acquisition. There was no association between TTP and mortality. A low TTP is associated with IE in E. faecalis bacteremia and could be used as a help in determining the need for echocardiography in patients with this condition.

Time to positivity (TTP) is the delay of time from incubation to blood culture positivity. Short TTP can predict mortality and source of infection. The aim of this study was to investigate the value of TTP of patients with bloodstream infections with enterococci (E-BSI).In a single centre retrospective cohort study in Germany, the data of 244 patients with monomicrobial E-BSI were analyzed with hospital mortality as the primary outcome of interest from January 1 2014 to December 31 2016. Mortality rate of patients with bloodstream infections (BSI) with E. faecalis was 16.7%, Vancomycin sensitive E. faecium (VSEfm) 26.7% and Vancomycin resistant E. faecium (VREfm) 38.2%. Cut-offs showed a significantly higher mortality rate when compared to longer TTP (E. faecalis: P=0.047; VSEfm: P=0.02), but were not risk factors in survival analysis (E.faecalis: HR (hazard ratio): 2.73; P=0.17; VSEfm: HR: 1.63; P=0.15; VREfm: HR: 1.24; P=0.63). TTP≤10.5 hours with E. faecalis BSI was a discriminator for cardiovascular source of infection (AUC: 0.75). A short TTP could predict mortality rates and source of infection but was not an independent parameter for risk of death in survival analysis.

(1) Background: Empirical antibiotics for suspected neonatal early-onset sepsis are often prolonged administered, even in the absence of clinical signs of infection, while awaiting the blood cultures results. The C-reactive protein is widely used to guide antibiotic therapy, although its increase in the first hours of life is not always evidence of infection. The aim of this study was to evaluate the time to positivity (TTP) of blood cultures (BC) that develop pathogens in our population of neonates and determine whether TTP could safely inform the decisions on empirical antibiotic discontinuation in neonatal early-onset sepsis and reduce the use of unnecessary antibiotics. (2) Methods: We retrospectively collected data of all newborns ≥ 34 weeks admitted to the Neonatal Intermediate-Care Unit at Policlinico “A. Gemelli” University Hospital (Rome, Italy) from 2014 to 2018, with suspected early-onset sepsis (EOS). The TTP was the time in hours from the first BC inoculation to the bacterial growth. We defined as positive BC only those with a pathogenic organism. (3) Results: In total, 103 out of 20,528 infants born in the five-year study period were admitted to our Neonatal Intermediate-Care Unit because of a suspected EOS and enrolled into the study. The mean TTP of pathogenic organisms was 17.7 ± 12.5 h versus 80.5 ± 55.8 h of contaminants (p = 0.003). We found ten positive BCs. The TTP of BC was lower than 12, 36, and 48 h in 80%, 90%, and 100% of cases, respectively. CRP levels on admission were similar in infants with a positive and negative BC (p = 0.067). The discontinuation of therapy in asymptomatic infants 48 h after initiation would have resulted in a saving of 217 days of antibiotics (31.1% of total days administered). (4) Conclusion: From our data, the TTP of blood cultures that develop pathogens is less than 48 h in 100% of cases. Therefore, in late preterm and full-term infants with suspected EOS, stopping empiric antibiotics 48 h after initiation may be a safe practice to reduce unnecessary antibiotic use, when blood cultures are negative and infants asymptomatic.

OBJECTIVES: To determine the time to positivity for bacterial pathogens and contaminants in blood and cerebrospinal fluid (CSF) cultures in a cohort of febrile infants ≤60 days of age. METHODS: This was a secondary analysis of prospective observational multicenter study of noncritically ill infants ≤60 days of age with temperatures ≥38°C and blood cultures (December 2008 to May 2013). The main outcome was time to positivity for bacterial pathogens and contaminants. RESULTS: A total of 256 of 303 (84.49%) patients with positive blood cultures, and 73 of 88 (82.95%) with positive CSF cultures met inclusion criteria. Median time (interquartile range [IQR]) to positivity for blood cultures was 16.6 hours (IQR 12.6–21.9) for bacterial pathogens (n = 74) and 25.1 hours (IQR 19.8–33.0) for contaminants (n = 182); P < .001. Time to bacterial pathogen positivity was similar in infants 0 to 28 days of age (15.8 hours [IQR 12.6–21.0]) and 29 to 60 days of age (17.2 [IQR 12.9–24.3]; P = .328). Median time to positivity for CSF was 14.0 hours (IQR 1.5–21.0) for bacterial pathogens (n = 22) and 40.5 hours (IQR 21.2–62.6) for contaminants (n = 51); P < .001. A total of 82.4% (95% confidence interval, 71.8–90.3) and 81.8% (95% confidence interval, 59.7%–94.8%) of blood and CSF cultures showed bacterial pathogen positivity within 24 hours. CONCLUSIONS: Among febrile infants ≤60 days of age, time to blood and CSF positivity was significantly shorter for bacterial pathogens than contaminants. Most blood and CSF cultures for bacterial pathogens were positive within 24 hours. With our findings, there is potential to reduce duration of hospitalization and avoid unnecessary antibiotics.

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.

Time to positivity (TTP) of blood cultures can guide antimicrobial therapy. This single-center retrospective cohort study aimed to determine the yield of clinically significant organisms from blood cultures that were initially negative at 24 hours. Clinically significant organisms were uncommon after 24 hours (1.5%) and more common in intensive care unit settings.

Objective To evaluate the application value of time to positivity (TTP) for blood culture combined with inflammatory parameters that included immature granulocyte percentage (IG%), immature granulocyte count (IG#), C‐reactive protein (CRP), white blood cells (WBC) neutrophil percentage (NE%), and neutrophil‐to‐lymphocyte ratio (NLR), and to identify bloodstream infections from contamination with coagulase‐negative staphylococci (CoNS) in pediatric patients. Methods Data of 12 897 inpatients with blood culture CoNS were retrospectively collected and analyzed from January‐December 2019 at our hospital. According to pre‐defined criteria, they were divided into a CoNS infection group (132 cases) and a CoNS contamination group (124 cases). Infection with Staphylococcus aureus (SA, 27 cases) at the same period was considered a positive control group. ROC curve analysis assisted in determining the value of applying TTP combined with the above‐mentioned inflammatory parameters to distinguish CoNS infection from contamination. Results Among the 256 strains of CoNS, Staphylococcus hominis (55.1%), Staphylococcus epidermidis (32.0%), and Staphylococcus capitis (7.0%) were common. There was no significant difference in the subspecies distribution between the infection and contamination groups. The TTP of the CoNS infection group was significantly lower than the contamination group (P, ROC analysis of TTP and inflammatory parameters in identifying CoNS bloodstream infection from contamination. A: ROC curve analysis of single indicators including IG%, IG#, CRP, NE%, and NLR. The AUC of TTP was the highest, reaching a value of 0.913, the AUC of IG% was 0.712, and the AUC of IG#, CRP, NE%, and NLR were 0.679, 0.645, 0.595, and 0.605, respectively, which were all evidently lower than 0.7. B: ROC curve analysis of TTP combined with inflammatory parameters. When TTP was combined with IG%, IG#, CRP, or NLR, the AUC was 0.951, 0946, 0.945, and 0.923, respectively. When TTP was combined with IG%, CRP, and NLR, the AUC was the highest, with a value of up to 0.977.

One of the reasons for the lengthy tuberculosis (TB) treatment is the difficulty to treat the nonmultiplying mycobacterial subpopulation. In order to assess the ability of (new) TB drugs to target this subpopulation, we need to incorporate dormancy models in our preclinical drug development pipeline. In most available dormancy models, it takes a long time to create a dormant state, and it is difficult to identify and quantify this nonmultiplying condition. The Mycobacterium tuberculosis 18b strain might overcome some of these problems, because it is dependent on streptomycin for growth and becomes nonmultiplying after 10 days of streptomycin starvation but still can be cultured on streptomycin-supplemented culture plates. We developed our 18b dormancy time-kill kinetics model to assess the difference in the activity of isoniazid, rifampin, moxifloxacin, and bedaquiline against log-phase growth compared to the nonmultiplying M. tuberculosis subpopulation by CFU counting, including a novel area under the curve (AUC)-based approach as well as time-to-positivity (TTP) measurements. We observed that isoniazid and moxifloxacin were relatively more potent against replicating bacteria, while rifampin and high-dose bedaquiline were equally effective against both subpopulations. Moreover, the TTP data suggest that including a liquid culture-based method could be of additional value, as it identifies a specific mycobacterial subpopulation that is nonculturable on solid media. In conclusion, the results of our study underline that the time-kill kinetics 18b dormancy model in its current form is a useful tool to assess TB drug potency and thus has its place in the TB drug development pipeline.

Introduction: A prolonged incubation time is generally recommended for diagnosing periprosthetic joint infections (PJI). However, in literature, no distinction is made between acute and chronic infections.Methods: All patients with a PJI that underwent surgical debridement between November 2015 and February 2019 with or without revision of the prosthesis were retrospectively evaluated. Synovial fluid, 5 intraoperative periprosthetic tissue samples, and the sonicated prosthesis were cultured.Results: Fifty-nine patients were analyzed, including 21 acute PJIs (33 isolates) and 38 chronic PJIs (46 isolates). In acute PJIs, all isolates grew within 5 days, while this took 11 days for chronic PJIs. Sonication fluid showed the shortest time to positivity (78% at day 2) for chronic PJIs, but no difference was observed for acute PJIs compared to tissue cultures.Conclusion: In contrast to cultures from chronic PJIs, acute PJIs do not need a prolonged incubation time and no clear benefit is observed for sonication. (C) 2020 The Authors. Published by Elsevier Inc.

A surge of patients with coronavirus disease 2019 (COVID-19) presenting to New York City hospitals in March 2020 led to a sharp increase in the utilization of blood cultures, which overwhelmed the capacity of automated blood culture instruments. We sought to evaluate the utilization and diagnostic yield of blood cultures during the COVID-19 pandemic to determine prevalence and common etiologies of bacteremia, and to inform a diagnostic approach to relieve blood culture overutilization. We performed a retrospective cohort analysis of 88,201 blood cultures from 28,011 patients at a multicenter network of hospitals within New York City to evaluate order volume, positivity rate, time to positivity, and etiologies of positive cultures in COVID-19. Ordering volume increased by 34.8% in the second half of March 2020 compared to the first half of the month. The rate of bacteremia was significantly lower among COVID-19 patients (3.8%) than COVID-19 negative patients (8.0%) and those not tested (7.1%), p < 0.001. COVID-19 patients had a high proportion of organisms reflective of commensal skin microbiota, reducing the bacteremia rate to 1.6% when excluded. More than 98% of all positive cultures were detected within 4 days of incubation. Bloodstream infections are very rare for COVID-19 patients, which supports the judicious use of blood cultures in the absence of compelling evidence for bacterial coinfection. Clear communication with ordering providers is necessary to prevent overutilization of blood cultures during COVID-19 surges, and laboratories should consider shortening the incubation period from 5 days to 4 days to free additional capacity.

Fast and accurate detection of causative agents of bloodstream infections remains a challenge of today's microbiology. We compared the performance of cutting‐edge technology based on polymerase chain reaction coupled with electrospray ionization‐mass spectrometry (PCR/ESI‐MS) with that of conventional broad‐range 16S rRNA PCR and blood culture to address the current diagnostic possibilities for bloodstream infections. Of 160 blood samples tested, PCR/ESI‐MS revealed clinically meaningful microbiological agents in 47 samples that were missed by conventional diagnostic approaches (29.4% of all analyzed samples). Notably, PCR/ESI‐MS shortened the time to positivity of the blood culture‐positive samples by an average of 34 hr. PCR/ESI‐MS technology substantially improved current diagnostic tools and represented an opportunity to make bloodstream infections diagnostics sensitive, accurate, and timely with a broad spectrum of microorganisms covered., By using the polymerase chain reaction coupled with electrospray ionization‐mass spectrometry (PCR/ESIMS) technology, we detected pathogenic agents in 29.4% (47 of 160) more samples than by using 16S rRNA PCR and/or blood culture. Thus, the PCR/ESI‐MS represented an opportunity to make the bloodstream infection diagnostics highly sensitive and accurate.

PURPOSE: We analyzed the workflow of the blood culture procedure with one blood culture incubator in the microbiology laboratory, in comparison with the workflow with the incubators systems placing outside, and in a microbiology laboratory without 24-h staffing. METHODS: We assessed the elapsed time (ET) and time-to-result (TTR) in the two laboratory workflows during 1 month period in consecutive years. First period with one BACT/ALERT 3D module located in the microbiology laboratory (ML) (access 8 a.m. to 10 p.m.) and second period with three BACT/ALERT VIRTUO modules (one located in ML and two in the core sample laboratory, access 24 h). RESULTS: The mean ET with BACT/ALERT 3D was 7.09 ± 6.15 h and 1.32 ± 3.14 h with BACT/ALERT VIRTUO. During the 8:00 a.m. to 10:00 p.m. shift, the average ETs were 3.54 ± 5.06 vs 1.59 ± 1.29 h for the two time periods, respectively. Since the automated loading of bottles on the BACT/ALERT VIRTUO allows processing of blood cultures during the night shift, there was a significant reduction of time during the 10:00 p.m. to 8:00 a.m. shift, where the average ET was 10.52 ± 5.23 vs 1.00 ± 4.40 h, respectively. The percentage of positivity in the first period was 9.03% and 11.18% in the second (p = 0.0003). The average TTR in the first period was 24.78 ± 15.9 h and 16.85 ± 14.13 h in the second (p

Setting Alcohol use increases the risk of tuberculosis (TB) disease and is associated with worse outcomes. Objective To determine whether alcohol use affects TB severity at diagnosis in a high-burden setting. Design Participants were smear-positive people living with TB (PLWTB) in India. Disease severity was assessed as 1) high versus low smear grade, 2) time to positivity (TTP) on liquid culture, 3) chest radiograph cavitation, and 4) percent lung affected. Alcohol use and being at-risk for alcohol use disorders (AUD) were assessed using the AUDIT-C. Univariable and multivariable analyses were conducted. Results Of 1166 PLWTB, 691 (59.3%) were drinkers; of those, 518/691 (75.0%) were at-risk for AUD. Drinkers had more lung affected than non-drinkers (adjusted mean difference 10.8%, p Conclusions A large proportion of PLWTB were drinkers and were at-risk for AUD. Alcohol drinkers had more lung affected than non-drinkers. Studies are needed to explore mechanisms of this association.

The usefulness of blood culture time-to-positivity (TTP) in the diagnosis of endovascular infections has previously been shown. Here, we investigated TTP in 41 patients with F. necrophorum bacteraemia and found an association between short TTP and Lemierre's syndrome (p = 0.026).

Background: Fast identification of Candida glabrata is important, because empirical antifungal therapy for fungemia with C. glabrata and non-C. glabrata varies. We proposed an algorithm for rapid presumptive diagnosis to identify fungemia with C. glabrata using earlier or only growth from anaerobic bottles and longer time to positivity (TTP) in blood cultures.Methods: Positivity and TTP using the BacT/Alert 3D system (bioMerieux Inc, USA) with resin bottles (FA Plus and FN Plus) were analyzed in 215 candidemia patients from June 2014 to June 2016 in a university- affiliated hospital in Korea.Results: A higher proportion of earlier or only growth from anaerobic bottles was observed in C. glabrata (38.8%, 7/18) than in C. albicans (7.6%, 8/105), C. parapsilosis (10.5%, 4/138), and C. tropicalis (9.2%, 5/54) (P=0.006). The mean (±standard deviation) TTP for C. glabrata was 41.7 h (±16.3 h) compared with 26.7 h (±15.9 h) for C. albicans, 33.4 h (±8.4 h) for C. parapsilosis, and 23.1 h (±17.3 h) for C. tropicalis (P31.4 h.Conclusion: This two-step algorithm in the BacT/Alert 3D system could be the basis for an initial empirical antifungal therapy for fungemia with C. glabrata prior to final identification. (Ann Clin Microbiol 2018;21:23-27)

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

The Carba NP test was developed to detect carbapenemase-producing Enterobacteriaceae, and uses imipenem as the reaction substrate. In Japan, IMP-6 metallo-β-lactamase (MBL) producers, which are usually resistant to meropenem but susceptible to imipenem, and IMP-1 MBL producers, which are usually resistant to both carbapenems are prevalent. We performed the Carba NP test with IMP-6 and IMP-1 MBL producers, and both types were detected by the Carba NP test with high sensitivity. All IMP-1 MBL producers were detected by the Carba NP test, but the minimum inhibitory concentrations (MICs) of imipenem varied from 0.25 to >32μg/mL, and the time to positivity varied from 0 to 30min. Time to positivity was significantly correlated with expression levels of blaIMP-1, but not with MICs of imipenem. These results suggested that the Carba NP test can be used as a screening assay for carbapenemase gene expression levels among producers of the same type of carbapenemase. Using this approach, it is possible to determine whether the carbapenem resistance of each carbapenemase-producing Enterobacteriaceae isolate is primarily due to carbapenemase production, or to another mechanism such as outer membrane impermeability.

Introduction Staphylococci is the most commonly isolated bacteria in blood cultures (BC), and is mostly regarded as contamination. However, the clinical relevance and characteristics of CNS other than Staphylococcus epidermidis (Non-SE-CNS) is still unknown. Methods For the purpose of clarifying the epidemiology and clinical significance of Non-Se-CNS infections, we retrospectively evaluated BC isolates of Non-Se-CNS at our institute from May 2013 to March 2017. Infections were defined as true bacteremia if (1) two or more positive BCs of the same species were present (or detection of the same species in another clinically relevant sample), (2) the patient had clinical symptoms as outlined in the Centers for Disease Control and Prevention's definition of primary blood stream infection8 and the symptoms or markers of inflammation (e.g., fever, symptoms, white cell counts, C-reactive protein, or procalcitonin) were improved after pathogen-directed therapy (e.g. either antibiotic therapy and/or removal of the foreign body in the case of catheter-related blood stream infections suspected) and (3) without any other infection. Results During the period, 279 patients with BC positive for Non Se–CNS were identified. 44 patients were excluded, either due to missing data or multiple pathogens in the same BC. Among the remaining 235 patients, 67 (29%) were categorized as true bacteremia (n = 43) or possible infections (n = 24). Resistance rate to methicillin among Non-SE-CNS is about 60%, which is lower than those among S. epidermidis of 78%. Conclusion About 30% of Non-Se-CNS isolates were clinically relevant in our study. Antibiotic susceptibility of Non-SE-CNS is quite different than those of S. epidermidis.

Anaerobes are an important but uncommon cause of bloodstream infections (BSIs). For pediatric patients, routine inclusion of an anaerobic blood culture alongside the aerobic remains controversial. We implemented automatic anaerobic blood culture alongside aerobic blood cultures in a pediatric emergency department (ED) and sought to determine changes in recovery of obligate and facultative anaerobes. This was a cohort study in a pediatric ED (August 2015 to July 2018) that began in February 2017. Blood culture positivity results for true pathogens and contaminants were assessed, along with a secondary outcome of time to positivity (TTP) of blood culture. A total of 14,180 blood cultures (5,202 preimplementation and 8,978 postimplementation) were collected, with 8.8% (456) and 7.1% (635) positive cultures in the pre- and postimplementation phases, respectively. Of 635 positive cultures in the postimplementation phase, aerobic blood cultures recovered 7.6% (349/4,615), whereas anaerobic blood cultures recovered 6.6% (286/4,363). In 211/421 (50.0%) paired blood cultures, an organism was recovered in both cultures. The number of cases where organisms were only recovered from an aerobic or an anaerobic bottle in the paired cultures were 126 (30.0%) and 84 (20.0%), respectively. The TTP was comparable regardless of bottle type. Recovery of true pathogens from blood cultures was approximately 7 h faster than recovery of contaminants. Although inclusion of anaerobic blood cultures only recovered 2 (0.69%) obligate anaerobes, it did allow for recovery of clinically significant pathogens that were negative in aerobic blood cultures and supports the routine collection of both bottles in pediatric patients with a concern of bloodstream infections.

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.This study aimed to evaluate TTP and DTTP to assess CVC-related yeast fungaemia (CVC-RYF).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.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 TTP10 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 DTTP5 hours had a sensitivity of 100% and a specificity of 71% for CVC-RYF.Since the median TTP was 17 hours and the most performing DTTP5 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.

The present study aimed to investigate the relationship between the time to positivity (TTP) of blood cultures and the performance of short-term subculture for MALDI-TOF MS-based identification of microorganisms from positive blood cultures in pediatric patients. The study was conducted between April 2018 and July 2019 at a tertiary children's hospital in Eastern China and the TTP of all the blood cultures included was retrospectively collected at the same time. In total, 332 monomicrobial blood cultures were included in the study. Blood cultures that were identified at the genus level (score ≥ 1.700) by the short-term subculture protocol had shorter TTP (median TTP: 17.5 h) than of those not identified (median TTP: 24.6 h; P

Background Pseudomonas aeruginosa (P. aeruginosa) is a major Gram-negative pathogen, which has been reported to result in high mortality. We aim to investigate the prognostic value and optimum cut-off point of time-to-positivity (TTP) of blood culture in children with P. aeruginosa bacteremia. Methods From August 2014 to November 2018, we enrolled the inpatients with P. aeruginosa bacteremia in a 1500-bed tertiary teaching hospital in Chongqing, China retrospectively. Receiver operating characteristic (ROC) analysis was used to determine the optimum cut-off point of TTP, and logistic regression were employed to explore the risk factors for in-hospital mortality and septic shock. Results Totally, 52 children with P. aeruginosa bacteremia were enrolled. The standard cut-off point of TTP was18 h. Early TTP (≤18 h) group patients had remarkably higher in-hospital mortality (42.9% vs 9.7%, P = 0.014), higher incidence of septic shock (52.4% vs12.9%, P = 0.06), higher Pitt bacteremia scores [3.00 (1.00–5.00) vs 1.00 (1.00–4.00), P = 0.046] and more intensive care unit admission (61.9% vs 22.6%, P = 0.008) when compared with late TTP (> 18 h) groups. Multivariate analysis indicated TTP ≤18 h, Pitt bacteremia scores ≥4 were the independent risk factors for in-hospital mortality (OR 5.88, 95%CI 1.21–21.96, P = 0.035; OR 4.95, 95%CI 1.26–27.50, P = 0.024; respectively). The independent risk factors for septic shock were as follows: TTP ≤18 h, Pitt bacteremia scores ≥4 and hypoalbuminemia (OR 6.30, 95%CI 1.18–33.77, P = 0.032; OR 8.15, 95%CI 1.15–42.43, P = 0.014; OR 6.46, 95% CI 1.19–33.19 P = 0.031; respectively). Conclusions Early TTP (≤18 hours) appeared to be associated with worse outcomes for P. aeruginosa bacteremia children.

Biomarkers for TB treatment response and outcome are needed. This study characterize changes in immune profiles during TB treatment, define biosignatures associated with treatment outcomes, and explore the feasibility of predictive models for relapse. Seventy-two markers were measured by multiplex cytokine array in serum samples from 78 cured, 12 relapsed and 15 failed treatment patients from South Africa before and during therapy for pulmonary TB. Promising biosignatures were evaluated in a second cohort from Uganda/Brazil consisting of 17 relapse and 23 cured patients. Thirty markers changed significantly with different response patterns during TB treatment in cured patients. The serum biosignature distinguished cured from relapse patients and a combination of two clinical (time to positivity in liquid culture and BMI) and four immunological parameters (TNF-β, sIL-6R, IL-12p40 and IP-10) at diagnosis predicted relapse with a 75% sensitivity (95%CI 0.38-1) and 85% specificity (95%CI 0.75-0.93). This biosignature was validated in an independent Uganda/Brazil cohort correctly classifying relapse patients with 83% (95%CI 0.58-1) sensitivity and 61% (95%CI 0.39-0.83) specificity. A characteristic biosignature with value as predictor of TB relapse was identified. The repeatability and robustness of these biomarkers require further validation in well-characterized cohorts.

Detection of coagulase-negative Staphylococcus in blood culture may be a result of either bacteremia or contamination. This often leads to diagnostic uncertainly. Our objective was to develop a method for differentiating whether a coagulase-negative Staphylococcus sp. positive blood culture represents bacteremia or contamination based on positive bottle detection pattern and time to positivity (TTP).This study included 155 and 51 adults with positive blood cultures for Staphylococcus epidermidis and Staphylococcus hominis, respectively, over a three-year period from 2016 to 2018. Positive blood culture cases were categorized as either bacteremia or contamination based on the clinically available information, and the detection pattern and TTP in each category were investigated.A total of 57, 92, and 6 S. epidermidis positive blood cultures were categorized as bacteremia, contamination, and undetermined, respectively, whereas 15 and 36 S. hominis positive blood cultures were categorized as bacteremia and contamination, respectively. For positive blood cultures categorized as bacteremia, all four bottles in two sets of blood cultures were positive in 47/47 S. epidermidis and 14/14 S. hominis, respectively, whereas either one bottle in each of two sets or three bottles in two sets were positive in 10/19 S. epidermidis and 1/4 S. hominis, respectively; most of those TTPs were48 h. Among them, the TTP in catheter-related blood stream infection was24 h.Although clinical assessment is crucial to differentiate between bacteremia and contamination, a combination of positive bottle detection pattern and TTP is a valuable diagnostic auxiliary tool.

The rapid diagnosis of bloodstream infection (BSI) often leads to better clinical outcomes. The present study was conducted to compare two rapid protocols (Sepsityper kit and short-term subculture) for matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS)-based identification of microorganisms from positive blood cultures in pediatric patients.This study was conducted between May 1, 2018, and April 30, 2019, at a tertiary children's hospital in eastern China. Only monomicrobial blood cultures included in this study were used to conduct the Sepsityper kit protocol and short-term subculture protocol at the same time.In total, 115 monomicrobial blood cultures were included in this study. For the Sepsityper kit protocol, 85.2% and 64.3% of microorganisms were correctly identified to the genus (score ≥ 1.700) and species levels (score ≥ 2.000), respectively. For the short-term subculture protocol, 89.6% and 70.4% of microorganisms were correctly identified to the genus and species levels, respectively. At the genus level (P = .321) or the species level (P = .325), there was no significant difference between the Sepsityper kit protocol and the short-term subculture protocol. Moreover, the short-term subculture protocol exhibited similar performance between Gram-positive bacteria (GPB) and Gram-negative bacteria (GNB) (the genus level: 93.7% (GPB) versus 87.9% (GNB), P = .518; the species level: 68.4% (GPB) versus 81.8% (GNB), P = .147). In addition, the Sepsityper kit protocol exhibited similar performance between GPB and GNB at the genus level (86.1% (GPB) versus 84.8% (GNB), P = 1.000). However, the Sepsityper kit protocol exhibited better performance in GNB at the species level (58.2% (GPB) versus 81.8% (GNB), P = .017). The rates of yeast-like fungi were correctly identified to the genus level (0.0%) or the species level (0.0%) for short-term subculture protocol were significantly lower than those of other microorganisms (the genus level: 92.0%, P = .001; the species level: 72.3%, P = .024). However, a similar result of identification was not found using the Sepsityper kit protocol (the genus level: P = .384; the species level: P = .599). In addition, the two rapid protocols both exhibited better performance at the genus level when the time to positivity (TTP) of blood cultures19 h (the Sepsityper kit protocol: 91.8% (TTP 19 h) versus 77.8% (TTP ≥ 19 h), P = .034; the short-term subculture protocol: 95.1% (TTP 19 h) versus 83.3% (TTP ≥ 19 h), P = .040). In addition, the two rapid protocols both exhibited better performance at the species level when the TTP of blood cultures was19 h (the Sepsityper kit protocol: 78.7% (TTP 19 h) versus 48.1% (TTP ≥ 19 h), P = .000; the short-term subculture protocol: 83.6% (TTP 19 h) versus 55.6% (TTP ≥ 19 h), P = .001).The Sepsityper kit protocol and short-term subculture protocol are both reliable and rapid methods for the identification of most microorganisms from positive blood cultures in pediatric patients. The performance of these two rapid protocols is associated with the TTP of blood cultures.