Search

Aim Methods Results Conclusions Continuous monitoring of blood culture (BC) systems allows rapid detection of microbial growth. We aimed to determine differences in time to positivity (TTP) in BACTEC BC between organisms and whether a 36‐h period was sufficient to detect all relevant pathogenic bacteria for children admitted to a tertiary care paediatric hospital.This was a retrospective audit of positive aerobic (AE) and anaerobic (AN) BC from paediatric inpatients with available TTP from 1 August 2016 to 2 January 2019. First positive BC per bacteraemia episode was analysed.Overall, 649 BC were positive, of which 480 first positive BC were analysed: 246 AE (51.3%) only, 216 paired (45%) (108 AE and 108 AN) and 18 AN (3.8%) only. There were 372 episodes of bacteraemia in 340 patients. Median age was 19 months (interquartile range (IQR): 1.25–60). Median TTP for AE and AN cultures was 13.20 (IQR: 9.84–18.48) and 13.92 h (IQR: 10.32–17.04), respectively. Organisms were GNR 49.7%, GPC 29.6%, contaminants 14.5%, mixed 3.0%, other 2.4% and yeast 0.8%. Streptococcus agalactiae had the fastest median TTP in AE and AN cultures, followed by Escherichia coli (AE 8.88 vs. 10.20 h). For paired AE and AN cultures, TTP was faster for AE versus AN cultures (13.36 vs. 14.52 h, P = 0.001). A 36‐h cut‐off time captured 97.7% AE BC and 99.1% AN BC with pathogens, and 86.5% AE BC and 91.7% AN BC with contaminants, respectively.GNR were the commonest pathogens in paediatric BC and faster growth was detected in AE versus AN cultures. By 36 h, >97.7% of BC were positive for pathogens versus 86.5% for contaminants. [ABSTRACT FROM AUTHOR]

Studies examining time to positivity (TTP) of blood cultures as a risk factor for death have shown conflicting results. The study objective was to examine the effect of TTP on all-cause-30-day case-fatality among a population-based cohort of patients with bloodstream infections (BSI). A retrospective cohort study including all residents of Queensland, Australia with incident monomicrobial BSI managed in the publicly funded healthcare system from 2000 to 2019 was performed. Clinical, TTP and all-cause 30-day case-fatality information was obtained from state-wide sources. A cohort of 88 314 patients was assembled. The median TTP was 14 hours, with 5th, 25th, 75th, and 95th percentiles of 4, 10, 20, and 53 hours, respectively. The TTP varied significantly by BSI aetiology. The 30-day all-cause case-fatality rate was 2606/17 879 (14.6%), 2834/24 272 (11.7%), 2378/20 359 (11.7%), and 2752/22 431 (12.3%) within the first, second, third, and fourth TTP quartiles, respectively (p < 0.0001). After adjustment for age, sex, onset, comorbidity, and focus of infection, TTP within 10 hours (first quartile) was associated with a significantly increased risk for death (odds ratio 1.43; 95% CI, 1.35–1.50; p < 0.001). After adjustment for confounding variables (odds ratio; 95% CI), TTP within the first quartile for Staphylococcus aureus (1.56; 1.41–1.73), Streptococcus pneumoniae (1.91; 1.49–2.46), β-hemolytic streptococci (1.23; 1.00–1.50), Pseudomonas species (2.23; 1.85–2.69), Escherichia coli (1.37; 1.23–1.53), Enterobacterales (1.38; 1.16–1.63), other Gram-negatives (1.68; 1.36–2.06), and anaerobes (1.58; 1.28–1.94) increased the risk for case-fatality. This population-based analysis provides evidence that TTP is an important determinant of mortality among patients with BSI. [ABSTRACT FROM AUTHOR]

ABSTRACTKlebsiella pneumoniae is a common causative pathogen of intra-abdominal infection with concomitant bacteraemia, leading to a significant mortality risk. The time to positivity (TTP) of blood culture is postulated to be a prognostic factor in bacteraemia caused by other species. Therefore, this study aimed to investigate the prognostic value of TTP in these patients. The single-centred, retrospective, observational cohort study was conducted between 1 July 2016 and 30 June 2021. All adult emergency department patients with diagnosis of intra-abdominal infection and underwent blood culture collection which yield K. pneumoniae during this period were enrolled. A total of 196 patients were included in the study. The overall 30-day mortality rate was 12.2% (24/196), and the median TTP of the studied cohort was 12.3 h (10.5–15.8 h). TTP revealed a moderate 30-day mortality discriminative ability (area under the curve 0.73, p 12 h, N = 109), patients in the early TTP (≤12 h, N = 87) group had a significantly higher risk of 30-day morality (21.8% vs. 4.6%, p

ABSTRACT Rapid and accurate identification of Staphylococcus aureus (SA) in blood culture specimens is crucial for timely clinical intervention. Traditional Gram staining methods, although widely accessible and cost-effective, exhibit variable sensitivities and specificities in the BACTEC system. We aimed to develop and validate the “STAPH score,” a novel semi-quantitative scoring system that integrates Gram stain morphology and time to positivity to differentiate SA from coagulase-negative staphylococci (CoNS) in blood cultures. We analyzed 148 blood culture specimens from septic patients. Each specimen was assessed independently by two examiners using Gram staining and the STAPH score, which assigns points based on five parameters: cluster size, time to positivity, aerobic enlargement, pint (three-dimensional appearance), and the presence of hemorrhage. Sensitivity and specificity were calculated for various cutoff points. Cohen’s kappa coefficient was used to assess inter-examiner agreement. Of the 148 specimens, 49 (33.1%) were identified as SA and 99 (66.9%) as CoNS. At a STAPH score cutoff of 3 points, the sensitivity was 93.9% (95% confidence interval [CI], 83.1%–98.7%) and specificity was 91.9% (95% CI, 84.7%–96.4%). The kappa coefficient at this cutoff was 0.67 (95% CI, 0.55–0.79). A STAPH score

In severe Coronavirus disease 2019 (COVID-19), bloodstream infections (BSIs) are an increasing cause of morbidity and mortality. In critically ill patients with COVID-19, we aimed to evaluate the prevalence, clinical profiles, and outcomes of BSIs. This single-center prospective investigation was conducted at a tertiary care hospital in Western India. All patients (>18 years of age) hospitalized in the intensive care unit (ICU) or ward with RT-PCR-confirmed COVID-19 were included. Demographic information, clinical proficiency, and antibiotic resistance patterns were assessed. Of the 550 patients admitted to the COVID ICU, subsequent BSIs occurred in 7.45% of patients. Gram-negative pathogens comprised a significant proportion of BSIs (53/73, 72.6%). The most frequent isolates were Klebsiella pneumoniae (22/73, 30.1%), Acinetobacter baumannii (11/73,15.06%), and Escherichia coli (7/23, 9.58%). In 57.8% of the cases, multidrug-resistant organisms (MDRO) were discovered. The Enterococcus and K. pneumoniae families comprise the majority of MDRO. Gram-negative bacteria (30.18% [16/53]) were resistant to carbapenems. Increased total leukocyte count, mechanical ventilation, and the presence of comorbidities were significantly associated with the incidence of BSIs. In COVID-19-linked BSIs, we discovered a high frequency of A. baumannii. Clinicians should be aware of potential BSIs in the presence of comorbidities, elevated leukocyte count, and mechanical ventilation. To improve the results, empirical antibiotics must be started promptly, and the situation must be de-escalated quickly. The most frequent isolates were A. baumannii and K. pneumoniae ([11/73, 15.06%] and [22/73, 30.1%], respectively). To reduce the incidence of MDRO, infection control procedures should be strictly followed in patients with multidrug resistance.

In severe Coronavirus disease 2019 (COVID-19), bloodstream infections (BSIs) are an increasing cause of morbidity and mortality. In critically ill patients with COVID-19, we aimed to evaluate the prevalence, clinical profiles, and outcomes of BSIs. This single-center prospective investigation was conducted at a tertiary care hospital in Western India. All patients (>18 years of age) hospitalized in the intensive care unit (ICU) or ward with RT-PCR-confirmed COVID-19 were included. Demographic information, clinical proficiency, and antibiotic resistance patterns were assessed. Of the 550 patients admitted to the COVID ICU, subsequent BSIs occurred in 7.45% of patients. Gram-negative pathogens comprised a significant proportion of BSIs (53/73, 72.6%). The most frequent isolates were Klebsiella pneumoniae (22/73, 30.1%), Acinetobacter baumannii (11/73,15.06%), and Escherichia coli (7/23, 9.58%). In 57.8% of the cases, multidrug-resistant organisms (MDRO) were discovered. The Enterococcus and K. pneumoniae families comprise the majority of MDRO. Gram-negative bacteria (30.18% [16/53]) were resistant to carbapenems. Increased total leukocyte count, mechanical ventilation, and the presence of comorbidities were significantly associated with the incidence of BSIs. In COVID-19-linked BSIs, we discovered a high frequency of A. baumannii. Clinicians should be aware of potential BSIs in the presence of comorbidities, elevated leukocyte count, and mechanical ventilation. To improve the results, empirical antibiotics must be started promptly, and the situation must be de-escalated quickly. The most frequent isolates were A. baumannii and K. pneumoniae ([11/73, 15.06%] and [22/73, 30.1%], respectively). To reduce the incidence of MDRO, infection control procedures should be strictly followed in patients with multidrug resistance. [ABSTRACT FROM AUTHOR]

The timely and accurate identification of causative agents is crucial for effectively managing fracture-related infections (FRIs). Among various diagnostic methods, the "time to positivity" (TTP) of cultures has emerged as a valuable predictive factor in infectious diseases. While sonication of implants and inoculation of blood culture bottles with sonication fluid have enhanced sensitivity, data on the TTP of this microbiological technique remain limited. Therefore, patients with ICM criteria for confirmed FRI treated at our institution between March 2019 and March 2023 were retrospectively identified and their microbiological records were analyzed. The primary outcome parameter was TTP for different microorganism species cultured in a liquid culture collected from patients with confirmed FRI. A total of 155 sonication fluid samples from 126 patients (average age 57.0 ± 17.4 years, 68.3% males) was analyzed. Positive bacterial detection was observed in 78.7% (122/155) of the liquid culture pairs infused with sonication fluid. Staphylococcus aureus was the most prevalent organism (42.6%). Streptococcus species exhibited the fastest TTP (median 11.9 h), followed by Staphylococcus aureus (median 12.1 h) and Gram-negative bacteria (median 12.5 h), all of which had a 100% detection rate within 48 h after inoculation. Since all Gram-negative pathogens yielded positive culture results within 24 h, it could be discussed if empirical antibiotic therapy could be de-escalated early and limited towards the Gram-positive germ spectrum if no Gram-negative pathogens are detected up to this time point in the context of antibiotic stewardship. [ABSTRACT FROM AUTHOR]

Background We aimed to determine the factors associated with sequential blood culture time to positivity (STTP) and validate the previously defined time to positivity (TTP) ratio threshold of 1.5 in predicting adverse disease outcomes and mortality of Staphylococcus aureus bacteremia (SAB). Methods We conducted an observational study of adult patients with SAB. The TTP ratio was calculated by dividing the TTP of the second blood culture by that of the first. Results Of 186 patients, 69 (37%) were female, with a mean age of 63.6 years. Median TTP was 12 hours (interquartile range [IQR], 10–15 hours) from the initial and 21 hours (17–29) from sequential blood cultures. Methicillin-resistant S aureus (MRSA)–infected patients had significantly shorter STTPs (P <.001) and lower TTP ratios (P <.001) compared to patients with methicillin-susceptible S aureus (MSSA). A significant correlation between initial and STTP was observed in patients with MRSA (r = 0.42, P =.002) but not in those with MSSA. A higher rate of native valve endocarditis (NVE) significantly correlated with a TTP ratio of ≤1.5 (odds ratio, 2.65 [95% confidence interval, 1.3–5.6]; P =.01). The subgroup having an initial TTP <12 hours combined with a TTP ratio ≤1.5 showed the highest prevalence of NVE. Conclusions The STTP varies based on methicillin susceptibility of S aureus isolate. This study suggests a potential clinical utility of the STTP to identify patients at a higher risk of NVE. However, prospective studies are required to validate these findings. [ABSTRACT FROM AUTHOR]

We propose a multi‐metric flexible Bayesian framework to support efficient interim decision‐making in multi‐arm multi‐stage phase II clinical trials. Multi‐arm multi‐stage phase II studies increase the efficiency of drug development, but early decisions regarding the futility or desirability of a given arm carry considerable risk since sample sizes are often low and follow‐up periods may be short. Further, since intermediate outcomes based on biomarkers of treatment response are rarely perfect surrogates for the primary outcome and different trial stakeholders may have different levels of risk tolerance, a single hypothesis test is insufficient for comprehensively summarizing the state of the collected evidence. We present a Bayesian framework comprised of multiple metrics based on point estimates, uncertainty, and evidence towards desired thresholds (a Target Product Profile) for (1) ranking of arms and (2) comparison of each arm against an internal control. Using a large public‐private partnership targeting novel TB arms as a motivating example, we find via simulation study that our multi‐metric framework provides sufficient confidence for decision‐making with sample sizes as low as 30 patients per arm, even when intermediate outcomes have only moderate correlation with the primary outcome. Our reframing of trial design and the decision‐making procedure has been well‐received by research partners and is a practical approach to more efficient assessment of novel therapeutics. [ABSTRACT FROM AUTHOR]

Background: Bloodstream infections (BSI) represent a common cause of sepsis and mortality in children. Blood culture (BC) is the gold standard for diagnosis of BSI. The low sensitivity of BC in the pediatric population is usually due to the small volume of blood used for inoculation and to the antibiotics used before sampling. Here, we explore the ways to effectively reduce antibiotic activity to maximize the chances of pathogen recovery, and to enhance the growth of microorganisms in lower blood volume and bacterial counts. Methods: The recovery of common pathogens causing blood stream infections was analyzed after exposure to cefoperazone/sulbactam, vancomycin, and caspofung by using resin-containing or not BacT/Alert PF Plus and BD FX400 peds plus pediatric bottles. The microbial growth in the resin-containing bottles was assessed using 0.5 colony-forming units (CFU) bacterial inoculum to mimic the bacteremia/fungemia condition. The usefulness of a diagnosis to confirm or exclude BSI was evaluated by lower than recommended blood culture sampling (102 CFU/mL, 0.3 mL). Results: Staphylococcus aureus (S. aureus), and Candida glabrata (C. glabrata) were recovered from 100% of two types of resin-containing bottles in the presence of a sufficient antibiotic dose, while Escherichia coli (E. coli) was not restored to 100% in BD FX400 peds plus pediatric bottles. The shorter TTD for S. aureus, C. glabrata, and E. coli were observed in antibiotic-containing BacT/Alert PF Plus bottles. Both the PF Plus and BD resin test bottles showed consistently good TTD performances to Gram-negative, Gram-positive, and yeast species in low inoculum levels, with the exception of S. aureus. The lower volume of blood inoculated into culture bottles hardly affected the growth of most bacteria, but optimized PF Plus resin-bottles accelerated the detection of infectious agents, especially S. aureus, Streptococcus pneumoniae, and C. glabrata. Conclusions: It is possible to enhance recovery from antibiotic-containing pediatric bottles and shorten TTD for the identification of pathogens by using the BacT/Alert blood culture system combination with new resin-containing media. [ABSTRACT FROM AUTHOR]

The timely and accurate identification of causative agents is crucial for effectively managing fracture-related infections (FRIs). Among various diagnostic methods, the “time to positivity” (TTP) of cultures has emerged as a valuable predictive factor in infectious diseases. While sonication of implants and inoculation of blood culture bottles with sonication fluid have enhanced sensitivity, data on the TTP of this microbiological technique remain limited. Therefore, patients with ICM criteria for confirmed FRI treated at our institution between March 2019 and March 2023 were retrospectively identified and their microbiological records were analyzed. The primary outcome parameter was TTP for different microorganism species cultured in a liquid culture collected from patients with confirmed FRI. A total of 155 sonication fluid samples from 126 patients (average age 57.0 ± 17.4 years, 68.3% males) was analyzed. Positive bacterial detection was observed in 78.7% (122/155) of the liquid culture pairs infused with sonication fluid. Staphylococcus aureus was the most prevalent organism (42.6%). Streptococcus species exhibited the fastest TTP (median 11.9 h), followed by Staphylococcus aureus (median 12.1 h) and Gram-negative bacteria (median 12.5 h), all of which had a 100% detection rate within 48 h after inoculation. Since all Gram-negative pathogens yielded positive culture results within 24 h, it could be discussed if empirical antibiotic therapy could be de-escalated early and limited towards the Gram-positive germ spectrum if no Gram-negative pathogens are detected up to this time point in the context of antibiotic stewardship.

Xianggui Yang,1,&ast; Mingquan Liu,1,&ast; Xuejing Yu,2 Zhenguo Wang,3 Ying Xu1 1Department of Laboratory Medicine, Clinical Medical College and the First Affiliated Hospital of Chengdu Medical College, Chengdu, Sichuan, People’s Republic of China; 2Department of Internal Medicine, Division of Cardiology, University of Texas Southwestern Medical Center, Dallas, TX, USA; 3Department of Stomatology, Clinical Medical College and the First Affiliated Hospital of Chengdu Medical College, Chengdu, Sichuan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xianggui Yang; Ying Xu, Tel/Fax +86-17358631230 ; +86-28-83016723, Email yxg204@163.com; yingxu@cmc.edu.cnBackground: Candidemia caused by Candida tropicalis has more serious adverse consequences and an even higher mortality. Time to positivity (TTP) has been widely used to identify microbial species, resistant microorganisms and distinguish real pathogens and pollutants. However, few studies have demonstrated TTP as a presumptive diagnosis of C. tropicalis in patients with candidemia.Patients and Methods: A retrospective study of 136 episodes of candidemia and simulated blood cultures with 314 episodes of confirmed Candida strains were applied to explore the role of TTPs in diagnosing C. tropicalis. TTPs were recorded as the shorter one if both aerobic and anaerobic vials were positive. Lastly, relationships were tested between TTPs and resistance and initial inocula concentration.Results: For the retrospective study, the mean of TTPs for C. tropicalis from 136 patients with candidemia was significantly shorter than other Candida species. The area under the receiver operating characteristics (ROC) curve was 0.8896 ± 0.030 with a sensitivity of 92.86% and a specificity of 77.87%, respectively, indicating TTPs with a cut-off value of < 25.50 h had a strong diagnostic power for C. tropicalis in patients with candidemia. Moreover, TTPs from 314 simulated blood cultures showed similar results as the retrospective study, demonstrating TTP is a powerful diagnostic tool in early diagnosing C. tropicalis in patients with candidemia. Additionally, our results showed no statistical significance between TTPs and initial inocula concentration and resistance of Candida species, suggesting initial inocula concentration does not impact TTPs, and TTPs may not be promising in predicting the resistance of all Candida species.Conclusion: TTP can be employed to early distinguish C. tropicalis from other Candida species in patients with candidemia, which is extremely helpful to initiate empiric antifungal treatments to improve clinical outcomes.Keywords: time to positivity, C. tropicalis, presumptive diagnosis, Candida species, candidemia

Time-to-positivity (TTP) may assist in predicting the outcome of candidaemia. We analysed a candidaemia dataset collected prospectively in Australia over 1 year (2014–2015). TTP was defined as the period from blood culture sampling to the blood culture flagging positive. Of 415 candidaemia episodes, overall, 30-day mortality was 29% (120/415); mortality with Candida albicans was 35% (59/169), C. glabrata complex, 37% (43/115), C. tropicalis, 43% (10/23), Pichia kudriavzevii 25% (3/12), and C. parapsilosis complex 7% (5/71). Each day of increased TTP multiplied the odds ratio (OR) of survival at 30 days by a factor of 1.32 [95% confidence interval (CI) 1.06–1.69]. Shorter TTP was associated with increased mortality, with 1-day TTP associated with 30-day mortality 37% (41/112) (95%CI: 28%–46%) and 5-day TTP 11% (2/18) (95%CI: 2%–36%). Lay Summary: Time-to-positivity is a measure that is available to clinicians when patients are identified as having candida in their bloodstream. Our data support the association of a shorter time to positivity with higher mortality. [ABSTRACT FROM AUTHOR]

The fear of missing sepsis episodes in neonates frequently leads to indiscriminate use of antibiotics, and prescription program optimization is suggested for reducing this inappropriate usage. While different authors have studied how to reduce antibiotic overprescription in the case of early onset sepsis episodes, with different approaches being available, less is known about late-onset sepsis episodes. Biomarkers (such as C-reactive protein, procalcitonin, interleukin-6 and 8, and presepsin) can play a crucial role in the prompt diagnosis of late-onset sepsis, but their role in antimicrobial stewardship should be further studied, given that different factors can influence their levels and newborns can be subjected to prolonged therapy if their levels are expected to return to zero. To date, procalcitonin has the best evidence of performance in this sense, as extrapolated from research on early onset cases, but more studies and protocols for biomarker-guided antibiotic stewardship are needed. Blood cultures (BCs) are considered the gold standard for the diagnosis of sepsis: positive BC rates in neonatal sepsis workups have been reported as low, implying that the majority of treated neonates may receive unneeded drugs. New identification methods can increase the accuracy of BCs and guide antibiotic de-escalation. To date, after 36–48 h, if BCs are negative and the baby is clinically stable, antibiotics should be stopped. In this narrative review, we provide a summary of current knowledge on the optimum approach to reduce antibiotic pressure in late-onset sepsis in neonates.

Objective: To investigate the predictive value of blood culture time to positivity (TTP) combined with procalcitonin (PCT) and neutrophil/lymphocyte ratio (NLR) on the risk of death in patients with Escherichia coli bloodstream infection (BSI). Methods:223 cases of patients with Escherichia coli BSI who were admitted to our hospital from January 2020 to June 2022 were selected, and they were divided into death group and survival group according to whether they died within 28 d of admission. Clinical data and blood culture TTP of patients were collected, and the PCT and NLR were detected. Multivariate Logistic regression was used to analyze the influencing factors of death in patients with Escherichia coli BSI. Receiver operating characteristic (ROC) curve was used to analyze the predictive value of TTP, PCT and NLR on the risk of death in patients with Escherichia coli BSI. Results: The mortality rate of 223patients with Escherichia coli BSI within 28 d after admission was 30.04%（67/223). The TTP of the death group was shorter than that of the survival group, and the PCT and NLR were higher than those of the survival group (all P＜0.001). Multivariate Logistic regression analysis showed that increased age, admission to intensive care unit (ICU), tracheal intubation/incision, increased PCT and increased NLR were independent risk factors for death in patients with Escherichia coli BSI, and prolonged TTP was an independent protective factor（P＜0.05）. ROC curve analysis showed that the area under curve of TTP, PCT and NLR combined to predict the death of patients with Escherichia coli BSI was greater than that of each index alone. Conclusions: Shortened TTP and increased PCT and NLR are associated with increased risk of death in patients with Escherichia coli BSI. The combination of TTP, PCT and NLR has a high value in predicting the risk of death in patients with Escherichia coli BSI. [ABSTRACT FROM AUTHOR]

The association between time to positivity (TTP) of blood culture and the clinical prognosis of patients with Klebsiella pneumoniae bloodstream infection (BSI) remains unclear. A retrospective study of 148 inpatients with BSI caused by K. pneumoniae was performed at Shanghai Tongji Hospital, China, from October 2016–2020. The total in-hospital fatality rate was 32%. The median TTP was 11.0 (7.7–16.1) h and the optimal cutoff for prediction of in-hospital mortality was 9.4 h according to the ROC curve. Early TTP (<9.4 h) was a risk factor for in-hospital mortality by univariate analysis (OR = 2.5, 95% CI 1.2–5.0, P = 0.01), but not by multivariate analysis (OR = 2.7, 95% CI 1.0–7.4, P = 0.06). Old age, serum creatinine, white blood cells, and C-reactive protein values were risk factors for in-hospital mortality by multivariate analysis. Early TTP was not a risk factor for septic shock (OR = 1.8, 95% CI 0.6–5.1, P = 0.27) or ICU admission (OR = 1.0, 95% CI 1.0–1.0, P = 0.32). In conclusion, the in-hospital fatality rate of patients with K. pneumoniae BSI was relatively high and associated with an early TTP of blood cultures. However, no increased risk of mortality, septic shock or ICU admission was evident in early TTP patients. [ABSTRACT FROM AUTHOR]

Abstract Background The value of time to positivity (TTP) on diagnosis for catheter-related bloodstream infection and distinguishment on bacteria group and infection source has been investigated. However, the relationship between TTP and patient outcome requires verification, and we performed a systematic review and meta-analysis. Methods We searched PubMed, EMBASE, CINAHL, Cochrane Library, Web of Science for publications associated with the topic. We included studies that researched the TTP on predicting patient mortality and septic shock. Quality assessment is performed with Critical Appraisal Skills Programme (CASP). The analysis is performed using Review Manager Version 5.0.24. on articles available for data extraction on the exact population of each outcome group. The existence of publication bias was assessed by funnel plots. Statistical heterogeneity was evaluated using the Cochran Q and $${I}^{2}$$ I 2 statistics. The outcome is reported as an odds ratio. PROSPERO registration: CRD42021272286. Results Twenty-four eligible studies were included in our study. Twenty-four in the mortality group and six in the septic shock group. Mortality is significantly associated with the short time to positivity group with an odds ratio of 2.98 (95% CI: 2.25–3.96, p-value

Blood cultures are the gold standard for detecting bacteremia. We have studied the time to positivity of blood cultures in our neonatal unit to reduce antibiotic doses in patients with a negative blood culture. Empirical antibiotic treatment of neonatal sepsis could be withdrawn 24 hours after obtaining blood cultures. [ABSTRACT FROM AUTHOR]

Deep tissue culture specimens obtained at the time of revision shoulder arthroplasty are commonly positive for Cutibacterium. Clinical interpretation of positive cultures can be difficult. This was a multi-institutional study evaluating the accuracy of cultures for Cutibacterium using positive control (PC) and negative control (NC) samples. The relationship between time to culture positivity and strength of culture positivity was also studied. Eleven different institutions were each sent 12 blinded samples (10 PC and 2 NC samples). The 10 PC samples included 2 sets of 5 different dilutions of a Cutibacterium isolate from a failed total shoulder arthroplasty with a probable periprosthetic infection. At each institution, the samples were handled as if they were received from the operating room. Specimen growth, time to culture positivity, and strength of culture positivity (based on semiquantitative assessment) were reported. A total of 110 PC samples and 22 NC samples were tested. One hundred percent of specimens at the 4 highest dilutions were positive for Cutibacterium. At the lowest dilution, 91% of samples showed positive findings. Cutibacterium grew in 14% of NC samples. Cutibacterium grew in PC samples at an average of 4.0 ± 1.3 days, and all of these samples showed growth within 7 days. The time to positivity was significantly shorter (P <.001) and the strength of positivity was significantly higher (P <.001) in true-positive cultures compared with false-positive cultures. This multi-institutional study suggests that different institutions may report highly consistent rates of culture positivity for revision shoulder arthroplasty samples with higher bacterial loads. In contrast, with lower bacterial loads, the results are somewhat less consistent. Clinicians should consider using a shorter time to positivity and a higher strength of positivity as adjuncts in determining whether a tissue culture sample is a true positive. [ABSTRACT FROM AUTHOR]

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.

Abstract 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.

Background Streptococcus pyogenes bacteremia is a severe condition with high mortality. Time to blood culture positivity (TTP) is known to predict the outcome in bacteremia with other pathogens. This study aimed to determine the association between TTP and outcome in S pyogenes bacteremia. Methods This retrospective observational cohort study comprised adults with S pyogenes bacteremia, identified through the laboratory database between 2015 and 2018, in the Region of Skåne, Sweden. Correlations between TTP and outcomes were investigated. Primary outcome was death within 30 days, and secondary outcomes were presence of sepsis or disease deterioration within the first 48 hours. Results A total of 347 episodes of S pyogenes bacteremia were identified, of which 61 were excluded, resulting in 286 included episodes. Median TTP was 10.4 (interquartile range, 8.4–11.4) hours. Thirty-day mortality was 10%. Median TTP was shorter in patients who died within 30 days compared to survivors (8.6 vs 10.4 hours; P <.001). In a multivariable logistic regression, shorter TTP was associated with 30-day mortality when adjusting for age, Charlson Comorbidity Index, and focus of infection (odds ratio, 3.7 [95% confidence interval, 1.2–11.3]; P =.02). There was no statistically significant difference in TTP between patients with sepsis within 48 hours and those who did not have sepsis. Additionally, there was no statistically significant difference in TTP between patients with disease deterioration compared to those who did not deteriorate. Conclusions Knowledge on TTP might be a tool to determine the prognosis of a given patient with S pyogenes bacteremia. [ABSTRACT FROM AUTHOR]

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<0.001). [ABSTRACT FROM AUTHOR]

Resuscitation-promoting factor D (RpfD) is a protein involved in the resuscitation of dormant bacteria. A new tuberculosis vaccine carrying the rpfD gene has been successfully constructed, pcDNA3.1-rpfD. It was demonstrated that this vaccine exhibits cellular and humoral immune responses. Therefore, within this study, the efficacy of this new vaccine candidate was evaluated using mycobacterial growth inhibition assay (MGIA). MGIA is a functional assay that measures the complex host immune response, peripheral blood mononuclear cell (PBMC) and splenocyte from BALB/c mice against mycobacteria. With BACTECTM MGITTM 960 automated system, the effect of vaccination on bacterial growth was reported as a time to positivity (TTP) in hours. The mean of TTP from the vaccinated group (both pcDNA3.1-rpfD and BCG) was higher than the negative control group. These results suggest that pcDNA3.1-rpfD may be effective in controlling tuberculosis growth and may provide a clue for the development of the tuberculosis vaccine. In addition, despite previous evidence that IFNγ was essential for tuberculosis immunity, IFNγ (interferon gamma) production was found not to be correlated with mycobacterial inhibition. Therefore, these findings offer an alternative method to evaluate vaccine candidates than the assessment using IFNγ only. [ABSTRACT FROM AUTHOR]

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 (< 10% mortality, 0–1 points), medium risk (10–20% mortality, 2 points), and high 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 < 0.01). 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. [ABSTRACT FROM AUTHOR]

Abstract 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.

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. [ABSTRACT FROM AUTHOR]

Abstract Background Staphylococcus aureus (S. aureus) is a common cause of bacteremia, which leads to significant morbidity and mortality. We investigated the relationship between time to positivity (TTP) and clinical outcomes in children with S.aureus bacteremia in the China. Methods A retrospective study of Staphylococcus aureus bacteremia inpatient was performed in Children’s Hospital of Chongqing Medical University in China between 29 January 2014 and 29 August 2017. TTP and clinical parameters were determined and analyzed. The receiver operating characteristic (ROC) curves were plotted for optimal cut-off selection, multivariate logistic regression tests were performed to evaluate the association between TTP and clinical outcomes. Results Overall, 84 cases were enrolled. We stated that in-hospital mortality is significantly higher in the early TTP (≤17 h) than in the late TTP (> 17 h) group (57.14% vs 7.14%, P = 0.000). Septic shock occurred in 57.14% of patients with early TTP and in 18.57% of patients with late TTP (P = 0.002). Detailed multivariate and statistical analysis revealed that early TTP, need for vasoactive agent were independent risk factors of in-hospital mortality; early TTP, need for vasoactive agent and APACHE II score ≥ 15 were independent risk factors of septic shock incidence in S. aureus bacteremia children. Conclusions Overall, TTP of ≤17 h appeared to correlate with the worse outcomes for S. aureus bacteremia children. These results have important implications in the assessments and management of pediatric S. aureus bacteremia in a clinical setting. Trial registration Retrospectively registered.

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. [ABSTRACT FROM AUTHOR]

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)

The aim of this study is to explore the prognostic values and optimal cutoff point of time to positivity (TTP) of blood culture in children with Klebsiella pneumoniae (K. pneumoniae) bloodstream infection. Ninety-four children with K. pneumoniae bloodstream infection hospitalized in Children's Hospital of Chongqing Medical University from April 2014 to January 2019 were enrolled retrospectively. TTP and risk factors were determined and analyzed by receiver operating characteristic (ROC) analysis and logistic regression analysis. The standard cutoff point of TTP was 13 h. Patients in early TTP (≤ 13 h) group had significantly higher in-hospital mortality (37.93% vs 6.15%, P = 0.000), higher incidence of septic shock (44.83% vs 6.15%, P = 0.000), higher proportion of PRISM III scores ≥ 10 (48.28% vs 20.00%, P = 0.005), and higher proportion of hypoalbuminemia on admission (44.83% vs 18.46%, P = 0.008). Multivariate analysis indicated PRISM III scores ≥ 10, early TTP, and hypoalbuminemia on admission were independent risk factors of in-hospital mortality (OR 8.36, 95% CI 1.80–38.92, P = 0.007; OR 5.85, 95% CI 1.33–25.61, P = 0.019; OR 5.73, 95% CI 1.30–25.22, P = 0.021, respectively) and septic shock (OR 14.04, 95% CI 2.63–75.38, P = 0.002; OR 11.26, 95% CI 2.10–60.22, P = 0.005; OR 10.27, 95% CI 2.01–52.35, P = 0.005, respectively). Conclusion: Early TTP (TTP ≤ 13 h), PRISM III scores ≥ 10, and hypoalbuminemia on admission appeared to be associated with worse outcomes for K. pneumoniae bloodstream infection children. What is Known: • Klebsiella pneumoniae bloodstream infection is an important cause of infectious disease morbidity and mortality worldwide in children. • Short duration of time to positivity indicated poor clinical outcomes. What is New: • Time to positivity ≤ 13 h, along with PRISM III scores ≥ 10 and hypoalbuminemia on admission, indicated higher in-hospital mortality and incidence of septic shock in Klebsiella pneumoniae bloodstream infection children. • The cut-off point of TTP in this pediatric study was much longer than that reported in adult patients. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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 were <48 h. Among them, the TTP in catheter-related blood stream infection was <24 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Summary: 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. [ABSTRACT FROM AUTHOR]

Abstract Background Speeding up identification and antimicrobial susceptibility testing (AST) is of foremost importance in the management of blood cultures. Here, we describe a simple, rapid, and standardized approach based on a very short-term incubation on solid medium from positive blood cultures followed by MALDI-TOF mass spectrometry identification and automated AST. The aim of the study was to evaluate the impact in the laboratory practice of this new procedure with respect to that previously used (standard method) by comparing TAT and cumulative percentage of final reports to clinicians. Results Compared with the standard method, the new procedure gave correct organism identification at genus or species level in 98.4% of monomicrobial samples. AST resulted in 97.7% essential agreement and 98.1% categorical agreement, with 0.9% minor errors, 1.0% major error, and 1.5% very major errors. The mean turnaround time to identification and AST was 61.4 h by using the new method compared to 83.1 h by using standard procedure. Concerning cumulative percentages of final reports, approximately a third of results were available at 48 h from the check-in of the sample when using the new procedure, whereas no final reports were ready at the same time with the standard method. Conclusions The new procedure allows faster and reliable results using a simple and standardized approach. Thus, it represents an important tool for a more rapid management of blood cultures when molecular methods are not available in the laboratory.

Background: Staphylococcus aureus (S. aureus) is a common cause of bacteremia, which leads to significant morbidity and mortality. We investigated the relationship between time to positivity (TTP) and clinical outcomes in children with S.aureus bacteremia in the China.Methods: A retrospective study of Staphylococcus aureus bacteremia inpatient was performed in Children's Hospital of Chongqing Medical University in China between 29 January 2014 and 29 August 2017. TTP and clinical parameters were determined and analyzed. The receiver operating characteristic (ROC) curves were plotted for optimal cut-off selection, multivariate logistic regression tests were performed to evaluate the association between TTP and clinical outcomes.Results: Overall, 84 cases were enrolled. We stated that in-hospital mortality is significantly higher in the early TTP (≤17 h) than in the late TTP (> 17 h) group (57.14% vs 7.14%, P = 0.000). Septic shock occurred in 57.14% of patients with early TTP and in 18.57% of patients with late TTP (P = 0.002). Detailed multivariate and statistical analysis revealed that early TTP, need for vasoactive agent were independent risk factors of in-hospital mortality; early TTP, need for vasoactive agent and APACHE II score ≥ 15 were independent risk factors of septic shock incidence in S. aureus bacteremia children.Conclusions: Overall, TTP of ≤17 h appeared to correlate with the worse outcomes for S. aureus bacteremia children. These results have important implications in the assessments and management of pediatric S. aureus bacteremia in a clinical setting.Trial Registration: Retrospectively registered. [ABSTRACT FROM AUTHOR]

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 < 0.001). Septic shock occurred in 58.30% of patients with early TTP and in 21.00% of patients with late TTP (P < 0.001). Independent risk factors of in-hospital mortality and septic shock in children with S. pneumoniae bacteremia included early TTP, need for invasive mechanical ventilation, and PRISM III score ≥ 10. Overall, TTP ≤ 12 h appeared to associate with the worse outcomes for children with S. pneumoniae bacteremia. [ABSTRACT FROM AUTHOR]

(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.

The time to positivity (TTP) of blood cultures has been considered a predictor of clinical outcomes for bacteremia. This retrospective study aimed to determine the clinical value of TTP for the prognostic assessment of patients with Escherichia coli bacteremia. A total of 167 adult patients with E.coli bacteremia identified over a 22-month period in a 3500-bed university teaching hospital in China were studied. The standard cut-off TTP was 11 h in the patient cohort. The septic shock occurred in 27.9% of patients with early TTP (⩽11 h) and in 7.1% of those with a prolonged TTP (>11 h) (P = 0.003). The mortality rate was significantly higher for patients in the early than in the late group (17.7% vs. 4.0%, P < 0.001). Multivariate analysis showed that an early TTP (OR 4.50, 95% CI 1.70-11.93), intensive care unit admission (OR 8.39, 95% CI 2.01-35.14) and neutropenia (OR 4.20, 95% CI 1.55-11.40) were independently associated with septic shock. Likewise, the independent risk factors for mortality of patients were an early TTP (OR 3.80, 95% CI 1.04-12.90), intensive care unit admission (OR 6.45; 95% CI 1.14-36.53), a Pittsburgh bacteremia score ⩾2 (OR 4.34, 95% CI 1.22-15.47) and a Charlson Comorbidity Index ⩾3 (OR 11.29, 95% CI 2.81-45.39). Overall, a TTP for blood cultures within 11 h appears to be associated with worse outcomes for patients with E.coli bacteremia. [ABSTRACT FROM AUTHOR]

Background Linezolid exhibits remarkable sterilizing effect in tuberculosis; however, a large proportion of patients develop serious adverse events. The congener tedizolid could have a better side-effect profile, but its sterilizing effect potential is unknown. Methods We performed a 42-day tedizolid exposure-effect and dose-fractionation study in the hollow fiber system model of tuberculosis for sterilizing effect, using human-like intrapulmonary pharmacokinetics. Bacterial burden was examined using time to positivity (TTP) and colony-forming units (CFUs). Exposure-effect was examined using the inhibitory sigmoid maximal kill model. The exposure mediating 80% of maximal kill (EC80) was defined as the target exposure, and the lowest dose to achieve EC80was identified in 10000-patient Monte Carlo experiments. The dose was also examined for probability of attaining concentrations associated with mitochondrial enzyme inhibition. Results At maximal effect, tedizolid monotherapy totally eliminated 7.1 log10CFU/mL Mycobacterium tuberculosis over 42 days; however, TTP still demonstrated some growth. Once-weekly tedizolid regimens killed as effectively as daily regimens, with an EC80free drug 0- to 24-hour area under the concentration–time curve-to-minimum inhibitory concentration (MIC) ratio of 200. An oral tedizolid of 200 mg/day achieved the EC80in 92% of 10000 patients. The susceptibility breakpoint was an MIC of 0.5 mg/L. The 200 mg/day dose did not achieve concentrations associated with mitochondrial enzyme inhibition. Conclusions Tedizolid exhibits dramatic sterilizing effect and should be examined for pulmonary tuberculosis. A tedizolid dose of 200 mg/day or 700 mg twice a week is recommended for testing in patients; the intermittent tedizolid dosing schedule could be much safer than daily linezolid. [ABSTRACT FROM AUTHOR]

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.Clinical Trials Registration: NCT01392911. [ABSTRACT FROM AUTHOR]

Early phase 2 tuberculosis (TB) trials are conducted to characterize the early bactericidal activity (EBA) of anti‐TB drugs. The EBA of anti‐TB drugs has conventionally been calculated as the rate of decline in colony forming unit (CFU) count during the first 14 days of treatment. The measurement of CFU count, however, is expensive and prone to contamination. Alternatively to CFU count, time to positivity (TTP), which is a potential biomarker for long‐term efficacy of anti‐TB drugs, can be used to characterize EBA. The current Bayesian nonlinear mixed‐effects (NLME) regression model for TTP data, however, lacks robustness to gross outliers that often are present in the data. The conventional way of handling such outliers involves their identification by visual inspection and subsequent exclusion from the analysis. However, this process can be questioned because of its subjective nature. For this reason, we fitted robust versions of the Bayesian nonlinear mixed‐effects regression model to a wide range of TTP datasets. The performance of the explored models was assessed through model comparison statistics and a simulation study. We conclude that fitting a robust model to TTP data obviates the need for explicit identification and subsequent “deletion” of outliers but ensures that gross outliers exert no undue influence on model fits. We recommend that the current practice of fitting conventional normal theory models be abandoned in favor of fitting robust models to TTP data. [ABSTRACT FROM AUTHOR]

Few studies analyzed the association between blood culture time to positivity (TTP) and risk of complicated nontyphoidal Salmonella (NTS) bacteremia. We conducted a retrospective study of 206 patients (aged 60.4 ± 17.4 years) with NTS bacteremia during a 30-month period. Complicated NTS bacteremia was defined as the presence of 30-day mortality, complicated infection requiring surgery or abscess drainage, or requirement of intensive care unit admission. Serogroup D (75.7%) was the predominant isolates. Malignancy (44.7%) was the most prevalent comorbidity. Patients with rapid TTP (<10 h) were more likely to have thrombocytopenia, septic shock, persistent bacteremia, complicated infection, and a higher intensive care unit admission rate. In multivariate logistic regression model, a TTP <10 h was an independent predictor for complicated NTS bacteremia (adjusted odd ratio, 5.683, 95% confidence interval, 2.396–13.482). Our study showed that blood culture TTP provides important diagnostic and prognostic information in the treatment of NTS bacteremia patients. [ABSTRACT FROM AUTHOR]

Background: Speeding up identification and antimicrobial susceptibility testing (AST) is of foremost importance in the management of blood cultures. Here, we describe a simple, rapid, and standardized approach based on a very short-term incubation on solid medium from positive blood cultures followed by MALDI-TOF mass spectrometry identification and automated AST. The aim of the study was to evaluate the impact in the laboratory practice of this new procedure with respect to that previously used (standard method) by comparing TAT and cumulative percentage of final reports to clinicians.Results: Compared with the standard method, the new procedure gave correct organism identification at genus or species level in 98.4% of monomicrobial samples. AST resulted in 97.7% essential agreement and 98.1% categorical agreement, with 0.9% minor errors, 1.0% major error, and 1.5% very major errors. The mean turnaround time to identification and AST was 61.4 h by using the new method compared to 83.1 h by using standard procedure. Concerning cumulative percentages of final reports, approximately a third of results were available at 48 h from the check-in of the sample when using the new procedure, whereas no final reports were ready at the same time with the standard method.Conclusions: The new procedure allows faster and reliable results using a simple and standardized approach. Thus, it represents an important tool for a more rapid management of blood cultures when molecular methods are not available in the laboratory. [ABSTRACT FROM AUTHOR]

Background: Sputum samples were collected from tuberculosis patients in a high tuberculosis incidence area in the Western Cape, South Africa. The aim of this study was to evaluate the performance and time to diagnosis of a genotypic drug susceptibility testing method.Methodology: During June 2000 and November 2003, a total of 1,540 samples were sent for drug susceptibility testing (DST) to the national health laboratory services, and of those, a phenotypic DST result was obtained for 1,373 samples whereas a genotypic DST result was obtained for 1,301 of 1,540 samples. Performance-based calculations were done on 1,244 samples for which both a phenotypic and genotypic DST result was available.Results: The reproducibility of the genotypic and phenotypic DST methods was 97% and 95%, respectively. The sensitivity and specificity of the genotypic DST method was 68% and 99% for Isoniazid and 87% and 99% for Rifampicin, respectively. Smear gradation was found to influence the performance of the genotypic DST method. The genotypic DST method gave accurate DST results for 75% of the samples within 20 days (range, 15-25), whereas the phenotypic DST results were only available for 75% of the samples after 38 days (range, 26-115) (p