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BACKGROUND: Hospitalized neonates are vulnerable to infection and have high rates of antibiotic utilization. METHODS: Fourteen South African neonatal units (seven public, seven private sector) assembled multidisciplinary teams involving neonatologists, microbiologists, pharmacists, and nurses to implement prospective audit and feedback neonatal antimicrobial stewardship (NeoAMS) interventions. The teams attended seven online training sessions. Pharmacists conducted weekday antibiotic prescription reviews in the neonatal intensive care unit and/or neonatal wards providing feedback to the clinical teams. Anonymized demographic and NeoAMS interventions data were aggregated for descriptive purposes and statistical analysis. FINDINGS: During the 20-week NeoAMS intervention in 2022, 565 neonates were enrolled. Pharmacists evaluated seven hundred antibiotic prescription episodes; rule-out sepsis (180; 26%) and culture-negative sepsis (138; 20%) were the most frequent indications for antibiotic prescription. For infection episodes with an identified pathogen, only 51% (116/229) of empiric treatments provided adequate antimicrobial coverage. Pharmacists recommended 437 NeoAMS interventions (0·6 per antibiotic prescription episode), with antibiotic discontinuation (42%), therapeutic drug monitoring (17%), and dosing (15%) recommendations most frequent. Neonatal clinicians' acceptance rates for AMS recommendations were high (338; 77%). Mean antibiotic length of therapy decreased by 24% from 9·1 to 6·9 days (0·1 day decrease per intervention week; P = 0·001), with the greatest decline in length of therapy for culture-negative sepsis (8·2 days (95% CI 5·7-11·7) to 5·9 days (95% CI 4·6-7·5); P = 0·032). INTERPRETATION: This neonatal AMS programme was successfully implemented in heterogenous and resource-limited settings. Pharmacist-recommended AMS interventions had high rates of clinician acceptance. The NeoAMS intervention significantly reduced neonatal antibiotic use, particularly for culture-negative sepsis. FUNDING: A grant from Merck provided partial support.

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(1) Background: Prematurity is a serious condition associated with long-term neurological disability. This study aimed to compare the neurodevelopmental outcomes of preterm neonates with or without sepsis. (2) Methods: This single-center retrospective case-control study included infants with birth weight < 1500 g and/or gestational age ≤ 30 weeks. Short-term outcomes, brain MRI findings, and severe functional disability (SFD) at age 24 months were compared between infants with culture-proven or culture-negative sepsis or without sepsis. A chi-squared test or Mann-Whitney U test was used to compare the clinical and instrumental characteristics and the outcomes between cases and controls. (3) Results: Infants with sepsis (all sepsis n = 76; of which culture-proven n = 33 and culture-negative n = 43) were matched with infants without sepsis (n = 76). Compared with infants without sepsis, both all sepsis and culture-proven sepsis were associated with SFD. In multivariate logistic regression analysis, SFD was associated with intraventricular hemorrhage (OR 4.7, CI 1.7-13.1, p = 0.002) and all sepsis (OR 3.68, CI 1.2-11.2, p = 0.021). (4) Conclusions: All sepsis and culture-proven sepsis were associated with SFD. Compared with infants without sepsis, culture-negative sepsis was not associated with an increased risk of SFD. Given the association between poor outcomes and culture-proven sepsis, its prevention in the neonatal intensive care unit is a priority.

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Introduction: Data on the overall impact of antibiotic modification following initial empiric prescription in both culture-positive and culture-negative critically ill patients are exiguous. Materials and methods: In a retrospective analysis of "ANT-CRITIC" study, we classified ICU patients receiving empirical antibiotics who remained in the ICU for >72 hours or till availability of culture results (whichever is longer) into five groups based on culture results and antibiotic modification: negative culture, no change (group I), positive culture, no change (group II), positive culture, de-escalation (group III), positive culture, escalation (group IV) and negative culture, antibiotic modification (group V). Baseline variables and clinical outcomes were compared. Logistic regression analysis was performed to look for independent variables associated with mortality. Results: 276 prescription episodes were analyzed. Group II was associated with worsening organ dysfunction at 72 hours, lower clinical cure rate at day 7, and higher hospital mortality. There was an independent association between group II prescription and hospital mortality [adjusted OR 2.774 (CI 1.178-6.533), p = 0.02]. Group III received longer duration of antibiotic (mean duration = 8.27 ± 4.11 days, median duration = 7 days [IQR 5-11]). Conclusion: Outcomes of critically ill infected patients differ significantly when they are classified based on culture result and antibiotic modification pattern. How to cite this article: Ghosh S, Singh A, Lyall A. Modification of Initial Empirical Antibiotic Prescription and its Impact on Patient Outcome: Experience of an Indian Intensive Care Unit. Indian J Crit Care Med 2023;27(8):583-589.

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PURPOSE: Herein, we identified whether the clinical outcomes differ according to secondary culture results in postoperative sepsis patients and determined the predictors of culture-negative sepsis after abdominal surgery based on the secondary culture results. METHODS: Patients who admitted to the intensive care unit(ICU) after surgery due to abdominal infection and diagnosed with postoperative sepsis were included. Culture tests were obtained from body fluids and drains. Primary culture test was performed immediately after surgery, and secondary culture test was performed within 48 h to 7days after surgery. The participants were divided into the culture-positive sepsis(CPSS) and the culture-negative sepsis group(CNSS) according to culture positivity, and the clinical outcomes were compared. The predisposing factors of secondary CNSS were determined using multiple logistic regression analysis. RESULTS: Among 83 participants, 51 patients (61.4%) showed secondary culture-positivity(2'CPSS) and 32 patients (38.6%) showed secondary culture-negativity(2'CNSS). ICU mortality and in-hospital mortality were not different between two groups, but the length of ICU and hospital stay were significantly longer in 2'CPSS. In multivariate analysis, non-bowel surgery [odds ratio(OR) = 6.934, 95% confidence interval(CI):1.609-29.884, p=0.009], no diabetes (OR = 4.027,95%CI:1.161-13.973, p=0.028), and the prolonged administration of preoperative antibiotics (OR = 1.187,95%CI:1.023-1.377, p=0.024) were revealed as significant predisposing factors of 2'CNSS. CONCLUSION: Mortality showed no difference according to secondary culture positivity in postoperative sepsis patients after abdominal surgery. If a patient underwent non-bowel surgery or had no diabetes or administered preoperative antibiotics for more than 3 days, the physician should pay more attention to clinical deterioration, even if the seconday culture results are negative.

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Bacterial sepsis and septic shock are associated with a high mortality, and when clinically suspected, clinicians must initiate broad-spectrum antimicrobials within the first hour of diagnosis. Thorough review of prior cultures involving multidrug-resistant (MDR) pathogens along with other likely pathogens should be performed to provide an appropriate broad-spectrum empiric antibiotic coverage. The appropriate antibiotic loading dose followed by individualized modification of maintenance dose should be implemented based on the presence of hepatic or renal dysfunction. Use of procalcitonin is no longer recommended to determine need for initial antibacterial therapy and for de-escalation. Daily reevaluation of appropriateness of treatment is necessary based on the culture results and clinical response. All positive cultures should be carefully screened for possible contamination or colonization, which may not represent the true organism causing the sepsis. Culture negative sepsis accounts for one-half of all cases, and de-escalation of initial antibiotic regimen should be done gradually in these patients with close monitoring.

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BACKGROUND: The host response in culture-negative sepsis (CnS) has been marginally explored upon emergency department (ED) admission. It would be of paramount importance to create a clinical prediction rule to support the emergency department physician in identifying septic patients who can be treated with antibiotics immediately without waiting time to draw cultures if they are unlikely to provide useful diagnostic information. METHODS: A multivariable logistic regression analysis was applied to identify the independent clinical variables and serum biomarkers of the culture-negative status among 773 undifferentiated septic patients. Those predictors were combined to build a nomogram predictive of CnS. RESULTS: The serum concentrations of six biomarkers, among the eight biomarkers assayed in this study, were significantly lower in the patients with CnS (449) than in those with culture-positive sepsis (324). After correction for co-variates, only mid-regional proadrenomedullin (MR-proADM) was found to be independently correlated with culture-negative status. Absence of diabetes, hemoglobin concentrations, and respiratory source of infection were the other independent clinical variables integrated into the nomogram-its sensitivity and specificity for CnS were 0.80 and 0.79, respectively. CONCLUSIONS: Low concentrations of MR-proADM were independently associated with culture-negative sepsis. Our nomogram, based on the MR-proADM levels, did not predict culture-negative status with reasonable certainty in patients with a definitive diagnosis of sepsis at ED admission.

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Introduction: De-escalation is the key to balance judicious antibiotic usage for life-threatening infections and reducing the emergence of antibiotic resistance caused by antibiotic overuse. Robust evidence is lacking regarding the safety of antibiotic de-escalation in culture negative sepsis. Materials and Methods: Children admitted to the PICU during the first 6 months of 2019 with suspected infection were included. Based on the clinical condition, cultures and septic markers, antibiotics were de-escalated or continued at 48-72 h. Outcome data like worsening of primary infection, acquisition of hospital acquired infection, level of ICU support and mortality were captured. Results: Among the 360 admissions, 247 (68.6%) children received antibiotics. After excluding 92 children, 155 children with 162 episodes of sepsis were included in the study. Thirty four episodes were not eligible for de-escalation. Among the eligible group of 128 episodes, antibiotics were de-escalated in 95 (74.2%) and continued in 33 (25.8%). The primary infection worsened in 5 (5.2%) children in the de-escalation group and in 1 (3%) in non de-escalation group [Hazard ratio: 2.12 (95%CI: 0.39-11.46)]. There were no significant differences in rates of hospital acquired infection, mortality or length of ICU stay amongst the groups. Blood cultures and assessment of clinical recovery played a major role in de-escalation of antibiotics and the clinician's hesitation to de-escalate in critically ill culture negative children was the main reason for not de-escalating among eligible children. Conclusion: Antibiotic de-escalation appears to be a safe strategy to apply in criticallly ill children, even in those with negative cultures.