Background: Early initiation of broad-spectrum antibiotic agents is a cornerstone of the care of necrotizing skin and soft tissue infections (NSTI). However, the optimal duration of antibiotic agents is unclear. We sought to characterize antibiotic prescribing patterns for patients with NSTI, as well as associated complications. Patients and Methods: Using an NSTI registry, we characterized antibiotic use at a quaternary referral center. Kaplan-Meier analyses were used to describe overall antibiotic duration and relative to operative source control, stratified by presence of other infections that independently influenced antibiotic duration. Factors associated with successful antibiotic discontinuation were identified using logistic regression. Results: Between 2015 and 2018, 441 patients received antibiotic agents for NSTI with 18% experiencing a complicating secondary infection. Among those without a complicating infection, the median duration of antibiotic administration was 9.8 days (95% confidence interval [CI], 9.2-10.5) overall, and 7.0 days after the final debridement. Perineal NSTI received fewer days of antibiotic agents (8.3 vs. 10.6) compared with NSTI without perineal involvement. White blood cell (WBC) count and fever were not associated with failure of antibiotic discontinuation, however, a chronic wound as the underlying infection etiology was associated with greater odds of antibiotic discontinuation failure (odds ratio [OR], 4.33; 95% CI, 1.24-15.1). Conclusions: A seven-day course of antibiotic agents after final operative debridement may be sufficient for NSTI without any secondary complicating infections, because clinical characteristics do not appear to be associated with differences in successful antibiotic discontinuation.

BACKGROUND: There is currently no consensus on optimal duration of antibiotic treatment in febrile neutropenia. We report on the clinical impact of implementation of antibiotic de-escalation and discontinuation strategies based on the Fourth European Conference on Infections in Leukaemia (ECIL-4) recommendations in high-risk hematological patients.
METHODS: We studied 446 admissions after introduction of an ECIL-4-based protocol (hereafter \"ECIL-4 group\") in comparison to a historic cohort of 512 admissions. Primary clinical endpoints were the incidence of infectious complications including septic shock, infection-related intensive care unit (ICU) admission, and overall mortality. Secondary endpoints included the incidence of recurrent fever, bacteremia, and antibiotic consumption.
RESULTS: Bacteremia occurred more frequently in the ECIL-4 group (46.9% [209/446] vs 30.5% [156/512]; P < .001), without an associated increase in septic shock (4.7% [21/446] vs 4.5% [23/512]; P = .878) or infection-related ICU admission (4.9% [22/446] vs 4.1% [21/512]; P = .424). Overall mortality was significantly lower in the ECIL-4 group (0.7% [3/446] vs 2.7% [14/512]; P = .016), resulting mainly from a decrease in infection-related mortality (0.4% [2/446] vs 1.8% [9/512]; P = .058). Antibiotic consumption was significantly reduced by a median of 2 days on antibiotic therapy (12 vs 14; P = .001) and 7 daily antibiotic doses (17 vs 24; P < .001) per admission period.
CONCLUSIONS: Our results support implementation of ECIL-4 recommendations to be both safe and effective based on real-world data in a large high-risk patient population. We found no increase in infectious complications and total antibiotic exposure was significantly reduced.

Objectives: Neonatal late-onset sepsis work-up is a frequent occurrence in every neonatal department. Blood cultures are the diagnostic gold standard, however, a negative culture prior to 48-72 h is often considered insufficient to exclude sepsis. We aimed to develop a decision tree which would enable exclusion of late-onset sepsis within 24 h using clinical and laboratory variables. Study Design: Infants evaluated for late-onset sepsis during the years 2016-2019, without major malformations, in a tertiary neonatal center were eligible for inclusion. Blood cultures and clinical and laboratory data were extracted at 0 and 24 h after sepsis work-up. Infants with bacteriologically confirmed late-onset sepsis were compared to matched control infants. Univariate logistic regression identified potential risk factors. A decision tree based on Chi-square automatic interaction detection methodology was developed and validated. Results: The study cohort was divided to a development cohort (105 patients) and a validation cohort (60 patients). At 24 h after initial evaluation, the best variables to identify sepsis were C-reactive protein > 0.75 mg/dl, neutrophil-to-lymphocyte ratio > 1.5 and sick-appearance at 24 h. Use of these 3 variables together with blood culture status at 24 h, enabled identification of all infants that eventually developed sepsis through the decision tree model. Our decision tree has an area under the receiver operating characteristic curve of 0.94 (95% CI: 0.90-0.98). Conclusions: In non-sick appearing infants with a negative blood culture at 24 h and normal laboratory values, sepsis is highly unlikely and discontinuing antibiotics after 24 h is a viable option.

Background: Procalcitonin (PCT), an important biomarker, can be used for the guidance of antibiotic therapy in respiratory infection. However, it has been a problem that some patients might need antibiotic therapy restart because of infection recurrence after antibiotic discontinuation. To date, there are very few literature on the study of risk factors accounting for infection recurrence. Purpose of this clinical study: 1) To study on antibiotic discontinuation in ventilator-associated pneumonia (VAP) under the guidance of PCT; 2) To evaluate the possible risk factors leading to infection recurrence and antibiotic reuse. Methods: Antibiotic discontinuation was performed when patients met the following criteria: (i) serum PCT<0.5 μg/L, (ii) temperature<38.5℃ and (iii) leukocyte count<15×109/L. Next, the patients were divided into infection recurrence group (infection recurring within 7 days after antibiotic discontinuation) or infection controlled group (no infection recurring after antibiotic discontinuation). Possible risk factors accounting for infection recurrence were evaluated using logistic regression analysis. Results: Of the eligible 51 patients with VAP, 20 patients suffered infection recurrence. Clinical pulmonary infection score (CPIS) and characteristics of tracheal secretions were the independent risk factors (P=0.045 and P=0.041, respectively), accounting for infection recurrence. Simplified CPIS≥5 served a certain predictive value for infection recurrence in VAP when physicians considered antibiotic discontinuation (The area under the receiver operating characteristic curve 0.781, specificity 90.3%, sensitivity 55.0%, positive predictive value 78.6% and negative predictive value 75.7%). At the time of antibiotic discontinuation, differences between the two groups were not statistically significant in the proportion of patients with a tracheotomy and in the culture results of endotracheal aspirates (including semi-quantitative results and whether pathogens were multidrug-resistant [MDR] strains). Conclusion: Simplified CPIS and characteristics of tracheal secretions can be used to predict infection recurrence following PCT-guided antibiotic discontinuation in VAP. These findings are important because physicians may not need to put too much care on semi-quantitative culture results of endotracheal aspirates and whether pathogens are MDRstrains. Trial registration: The registration number of this clinical trial is: ChiCTR-OPC-17011228 (Trial registry name: Chinese Clinical Trial Registry; URL: http://www.chictr.org.cn).

Background We wanted to determine the impact of combined Clinical Pulmonary Infection Score (CPIS) and a spot serum procalcitonin (PCT)-guided protocol to shorten the duration of antibiotic treatment in patients with ventilator-associated pneumonia (VAP), mainly caused by nonfermentative gram-negative bacilli (NF-GNB). Methods Patients with VAP who received appropriate antibiotics for 7 days, temperature ⩽ 37.8°C, without shock, and CPIS ⩽ 6 were allocated to the PCT group or conventional group according to the treating physicians\' decisions. In the PCT group, antibiotics were stopped if the PCT level on day 8 < 0.5 ng/ml. In the conventional group, antibiotics were stopped according to physicians\' discretion. Results There were 24 patients in the PCT group and 26 patients in the conventional group. NF-GNB were responsible for VAP in 79.2% of the PCT group and 65.4% of the conventional group. PCT group had a greater number of antibiotic-free days alive during the 28 days after VAP onset than the conventional group (14.6 ± 5.4 days versus 5.9 ± 5.7 days, respectively; p <.001). In the multivariate, propensity score-adjusted analysis, the PCT group [coefficient = -9.1 (-12.2 to -6); p <.001] and extrapulmonary infections [coefficient = 6.4 (3.3-9.5); p <.001] were independent predictors of total antibiotic exposure days. There was no relapse in both groups. Meanwhile, 12.5% of the PCT group and 26.9% of the conventional group subsequently developed recurrent VAP compatible with superinfections. Conclusions CPIS and a spot serum PCT level appeared effective and safe to guide discontinuation of antibiotic treatment in patients with VAP caused by NF-GNB.
TCTR20160726002.

Based on recommendations of the ECIL-4, we prospectively evaluated discontinuation of empirical antibiotic therapy in high-risk neutropenic acute myeloid leukaemia patients with fever of unknown origin. Seven patients (median neutropenia duration 30 days) were included. Four of them remained afebrile but quickly recovered from neutropenia. The other three had rapid recurrent fever. Two of these three patients had bacteraemia with susceptible strains and one of them was transferred to the ICU for septic shock. Median duration of sparing of antibiotics for the seven patients was 3 days (2-4). Because of these limited results the study was stopped.