Genus Shewanella: A Potential Intestinal Colonizer Associated With Post-Operative Surgical Site Infections in Coastal Regions.

Background: This study aims to elucidate the clinical characteristics of Shewanella-related surgical site infections (SSIs) and assess the risk of mortality in patients by establishing a predictive model. Patients and Methods: A retrospective analysis of medical history and laboratory data of Shewanella-related SSI patients over the past decade was conducted via the electronic medical record (EMR) system. A predictive model for mortality risk in Shewanella-related SSI patients was established using plasma interleukin-6 (IL-6) levels combined with the Howell-PIRO scoring system. Results: Over the past 10 years, 45 strains of Shewanella were isolated from specimens such as bile, drainage fluid, and whole blood in patients with digestive tract SSIs. Among them, 21 of 45 (46.67%) patients underwent malignant tumor resection of the digestive system, 14 of 45 (31.11%) underwent endoscopic retrograde cholangiopancreatography (ERCP) common bile duct exploration or the stone removal, and seven of 45 (15.56%) were trauma repair patients with fractures and abdominal injuries. Among the 45 Shewanella-related SSI patients, 10 died within 30 days of infection, six cases involved infections with more than two other types of bacteria. The combined use of IL-6 and Howell-PIRO scores for mortality risk assessment yielded an receiver operating characteristic (ROC) curve with an area under the curve (AUC) of 0.9350, a positive predictive value of 92.71%, a negative predictive value of 94.58%, a diagnostic sensitivity of 95.35%, and a diagnostic specificity of 92.14%-all higher than the model using IL-6 or Howell-PIRO scores alone. Conclusions: We found that residents in coastal areas faced an increased risk of Shewanella-related SSI. Moreover, the higher the number of concurrent microbial infections occurring alongside Shewanella-related SSI, the greater the mortality rate among patients. The combined application of plasma IL-6 levels and the Howell-PIRO scoring system is beneficial for assessing patient mortality risk and guiding timely and proactive clinical interventions.

Intraventricular or intrathecal polymyxin B for treatment of post-neurosurgical intracranial infection caused by carbapenem-resistant gram-negative bacteria: a 8-year retrospective study.

PURPOSE: Post-neurosurgical intracranial infection caused by carbapenem-resistant gram-negative bacteria (CRGNB) is a life-threatening complication. This study aimed to assess the current practices and clinical outcomes of intravenous (IV) combined with intraventricular (IVT)/intrathecal (ITH) polymyxin B in treating CRGNB intracranial infection. METHODS: A retrospective study was conducted on patients with post-neurosurgical intracranial infection due to CRGNB from January 2013 to December 2020. Clinical characteristics and treatment outcomes were collected and described. Kaplan-Meier survival and multivariate logistic regression analyses were performed. RESULTS: The study included 114 patients, of which 72 received systemic antimicrobial therapy combined with IVT/ITH polymyxin B, and 42 received IV administration alone. Most infections were caused by carbapenem-resistant Acinetobacter baumannii (CRAB, 63.2%), followed by carbapenem-resistant Klebsiella pneumoniae (CRKP, 31.6%). Compared with the IV group, the IVT/ITH group had a higher cerebrospinal fluid (CSF) sterilization rate in 7 days (p < 0.001) and lower 30-day mortality (p = 0.032). In the IVT/ITH group, patients with CRKP infection had a higher initial fever (p = 0.014), higher incidence of bloodstream infection (p = 0.040), lower CSF sterilization in 7 days (p < 0.001), and higher 30-day mortality (p = 0.005) than those with CRAB infection. Multivariate logistic regression analysis revealed that the duration of IVT/ITH polymyxin B (p = 0.021) was independently associated with 30-day mortality. CONCLUSIONS: Intravenous combined with IVT/ITH polymyxin B increased CSF microbiological eradication and improved clinical outcomes. CRKP intracranial infections may lead to more difficult treatment and thus warrant attention and further optimized treatment.

A decade of neonatal sepsis in Stockholm, Sweden: Gram-positive pathogens were four times as common as Gram-negatives.

PURPOSE: To assess Gram-positive bacterial (GPB) bloodstream infection (BSI) in neonates, covering incidence, morbidity, mortality, antimicrobial resistance patterns and biomarkers in Region Stockholm, Sweden between 2006 and 2016. METHODS: A population-based retrospective epidemiological study including infants with GPB-BSI, admitted to the neonatal units at Karolinska University Hospital (KUH). Data were collected from patient records, the Swedish Neonatal Quality Register, the microbiological laboratory at KUH and the Swedish Public Health Agency. RESULTS: We identified 357 infants with GPB-BSI, representing an incidence of 1.47/1000 live births (LB). Group B streptococcus (GBS) was the most common pathogen causing BSI in full-term infants and early-onset sepsis (EOS) (0.20/1000 LB), while coagulase-negative staphylococci (CoNS) were predominant in infants born very preterm and in late-onset sepsis (LOS) (0.79/1000 LB). There were no fatal GBS BSI cases, but 10.2% developed meningitis. The GPB case fatality rate was 9.5% and the sepsis fatality rate 2.8%. In GPB-BSI, 1/10 did not have an elevated C-reactive protein level. Staphylococcus aureus (S. aureus) BSI increased during the study period, but no methicillin or vancomycin resistant strains were found. The antimicrobial resistance (AMR) rate was highest in CoNS isolates. CONCLUSION: GPB-BSI was four times more common than Gram-negative BSI in neonates but resulted in lower mortality rate. GBS was the most common pathogen in full-term infants and in EOS. CoNS was the most common pathogen in LOS and infants born very preterm, and the AMR rate was high in these isolates. The increasing trend of S. aureus BSI indicates a need of further investigation.

Intravenous fosfomycin in combination regimens as a treatment option for difficult-to-treat infections due to multi-drug-resistant Gram-negative organisms: A real-life experience.

AIM: To investigate the efficacy of intravenous (IV) fosfomycin as combination therapy for treatment of difficult-to-treat (DTT) acute and subacute infections with multi-drug-resistant (MDR) Gram-negative bacteria (GNB), and risk factors associated with 90-day mortality. METHODS: A retrospective, observational, monocentric study enrolled patients treated with IV fosfomycin in combination regimens (≥72 h) for proven DTT-MDR-GNB infection. Multi-variate regression analysis identified independent risk factors for 90-day mortality. A propensity score for receiving fosfomycin was performed to control for confounding factors. RESULTS: In total, 70 patients were included in this study: 54.3% had carbapenem-resistant isolates, 31.4% had ceftazidime/avibactam-resistant isolates and 28.6% had ceftolozane/tazobactam-resistant isolates. The main pathogens were Pseudomonas aeruginosa (57.1%) and Klebsiella pneumoniae (22.9%). The most prevalent infections were nosocomial pneumonia (42.9%), osteomyelitis (17.1%) and intra-abdominal infections. All-cause 30- and 90-day mortality were 15.7% and 31.4%, respectively (18.9% and 50% considering acute DTT-MDR-GNB infections alone). Relapse at 30 days occurred in 22.9% of cases (29% with emergence of fosfomycin resistance). Mortality at 90 days was independently associated with septic shock and ceftolozane/tazobactam resistance. The relationship between resistance to ceftolozane/tazobactam and 90-day mortality was confirmed to be significant after adjustment by propensity score analysis (hazard ratio 5.84, 95% confidence interval 1.65-20.68; P=0.006). CONCLUSIONS: Fosfomycin seems to be a promising salvage, combination treatment in DTT-MDR-GNB infections. Resistance to ceftolozane/tazobactam seems to be independently associated with treatment failure. Randomized clinical trials focusing on pathogen and infection sites are needed urgently to demonstrate the superiority of fosfomycin in combination with other agents for the resolution of DTT-MDR-GNB infections.

Mortalidad en niños con bacteriemia por Stenotrophomonas maltophilia: revisión sistemática / Mortality in children with Stenotrophomonas maltophilia-related bacteremia: A systematic review

Introducción: En los niños, la bacteriemia por Stenotrophomonas maltophilia es considerada una complicación severa y asociada a una elevada mortalidad. Con el objetivo de conocer la mortalidad asociada a esa condición, se realizó una revisión sistemática de la literatura. Material y métodos: Se aplicó una estrategia de búsqueda bibliográfica con las palabras clave: bacteriemia por Stenotrophomonas maltophilia, niños y adolescentes como únicos filtros. Se informan la mediana y los valores intercuartílicos de la frecuencia de la mortalidad reportada por los estudios incluidos. Resultados: Se identificaron 165 estudios potencialmente útiles. De ellos, se seleccionaron finalmente, 9 estudios para ser incluidos. La incidencia de mortalidad a consecuencia de una bacteriemia por S.maltophilia fue del 25%; Q25: 11­Q75: 36; rango: 6,06 a 40,6. Consideraciones finales: La bacteriemia por Sm tuvo un alto porcentaje de mortalidad en especial en pacientes con patología subyacente y uso de procedimientos invasivos y el uso inadecuado de antibióticos empíricos (AU)

Introduction: In children, Stenotrophomonas maltophilia-related bacteremia is considered a severe complication associated with high mortality. With the aim to determine the mortality associated with this condition, a systematic review of the literature was conducted. Material and methods: A literature search strategy was applied using the keywords: bacteremia due to Stenotrophomonas maltophilia, children, and adolescents as the only filters. The median and interquartile ranges of the mortality rates described in the studies included are reported. Results: A total of 165 potentially useful studies were identified, of which nine were finally selected to be included in the analysis. The incidence of S.maltophilia bacteremia-related mortality was 25%; Q25: 11­Q75: 36; range: 6.06 to 40.6. Final considerations: S.maltophilia-related bacteremia was associated with a high mortality rate especially in patients with an underlying disease, when invasive procedures were performed, and when emperical antibiotics were inadequately used (AU)

Assessment the efficacy of some various treatment methods, in vitro and in vivo, against Aeromonas hydrophila infection in fish with regard to side effects and residues.

Aeromonas hydrophila is an opportunistic bacteria with an overwhelming impact on fish farming industry especially with upraising of drug resistant mutants. This study aimed to evaluate and compare the therapeutic and side effects of levofloxacin (LEV), chitosan-nanoparticles (CNPs), and fructooligosaccharides (FOS) in control of this infection in tilapia. A total of 160 Nile-tilapia divided into 8-groups; G1: negative-control, G2: infected-control, G3: non-infected-(levofloxacin (LEV) 10 mg/kg bwt), G4: non-infected-(chitosan-nanoparticles (CNPs) 1 g/kg ration), G5: non-infected-(fructooligosaccharides (FOS) 20 g/kg ration), G6: infected-LEV, G7: infected-CNPs and G8: infected-FOS for 7 days. MICs were (0.125 µg/ml and 1.25 mg/ml) for LEV and CNPs respectively. No mortalities or significant adverse effects were recorded in non-infected treated-groups while infected were (20%) LEV, (30%) CNPs, (40%) FOS and (70%) G2. Aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP) decreased by LEV and CNPs than FOS while all increased total protein (TP) and albumin than G2. Malondialdehyde (MDA) significantly decreased and superoxide dismutase (SOD) and reduced glutathione (GSH) increased in all infected-treated groups than G2 in various degrees. Urea and creatinine descending order were FOS, LEV then CNPs decreased significantly than G2. LEV musculature residues, using HPLC, decreased gradually till the 5th day; 621.00 ± 0.66, 270.00 ± 0.48 then 64.00 ± 0.40, and 471.00 ± 0.79, 175.00 ± 0.52 ppb then not detected at 1st, 3rd, and 5th days of withdrawal in non-infected and infected groups respectively. Finally, LEV and CNPs were superior as bactericidal, decreasing mortalities and enzyme activities while CNPs and FOS increased performance, non-specific immunity, and antioxidant biomarkers.

Impact of polymyxin B hemoperfusion therapy on high endotoxin activity level patients after successful infection source control: a prospective cohort study.

We sought to evaluate the clinical implication of endotoxin levels in gram-negative bacilli (GNB)-induced abdominal septic shock patients with polymyxin B-hemoperfusion (PMX-HP) treatment. A prospective cohort of 60 patients who received surgical infectious source control for abdominal sepsis from January 2019 to December 2020 was included in the study. Endotoxin activity (EA) levels and Sequential Organ Failure Assessment (SOFA) scores were assessed immediately after surgery (baseline), 24, and 48 h post baseline. With receiver operating characteristic curves, the patients were stratified into two groups by the EA cut-off value (high-risk group vs low-risk group) and the clinical outcomes were compared. Logistic regression was performed to identify the clinical impact of PMX-HP on in-hospital death. Among the 31 high-risk patients (EA level ≥ 0.54), 16 patients (51.6%) received PMX-HP treatment and showed significant decreases in EA levels compared to patients who underwent conventional treatment only (- 0.34 vs - 0.12, p = 0.01). SOFA scores also showed significant improvement with PMX-HP treatment (12.8-8.9, p = 0.007). Fourteen in-hospital deaths occurred (45.2%), and PMX-HP treatment had a protective effect on in-hospital death (odds ratio (OR) 0.04, p = 0.03). In 29 low-risk patients (EA level < 0.54), seven patients (24.1%) received PMX-HP treatment and showed significant decreases in EA levels (0.46-0.16, p = 0.018). However, SOFA scores and in-hospital deaths were not improved by PMX-HP treatment. EA level significantly decreased after PMX-HP treatment and it may represent a therapeutic option to improve organ impairment and in-hospital death in septic shock patients with EA levels exceeding 0.54.

Oral administration of Sargassum polycystum extracts stimulates immune response and increases survival against Aeromonas hydrophila infection in Oncorhynchus mykiss.

This study investigated the immunomodulatory effects of Sargassum polycystum extract administration in rainbow trout (Oncorhynchus mykiss). S. polycystum methanolic extract was administered orally using feeding needles to individual rainbow trout at the dose of 0 (control), 1 (S1), 3 (S3) and 5 (S5) mg/100 µl/per fish twice a day for 7 days. On 1st, 5th, 3rd and 7th day, blood and tissues were collected from the fish and changes in humoral immune responses and immune-related gene expressions were determined. The result of oxidative radical production showed no difference during early stage of the experiment and was lately decreased (P < 0.05). Lysozyme activity increased on 3rd and 7th day of the study in S5 fish group and on 5th day in S3 group compared to control (P < 0.05). Myeloperoxidase activity had an increased level on the 1st and 3rd day in S1, S5 and S5 fish groups, respectively. IL-1ß gene was significantly up-regulated in kidney and intestine in all experimental groups (except on the 1st day, in the intestine of S5 fish group) compared to control (P < 0.05). IL-8 gene expression was elevated on 1st and 3rd day in kidney of all experimental fish groups. IL-6 transcript enhanced in a dose-dependent manner on 3rd and 7th day. IL-10 and IL-12 genes were also up-regulated. Survival in all treated fish groups challenged with Aeromonas hydrophila was significantly increased compared to that of control. The highest survival rate was recorded in S5 fish group (83.65%) followed by S3 fish group (82.62%). Our results suggest that S. polycystum aqueous methanolic extract is an effective immunostimulant and provide protection against A. hydrophila infection in rainbow trout at a dose of 3-10 mg/20 g body weight/day.

Clinical outcomes of combination versus monotherapy for gram negative non-HACEK infective endocarditis.

The objective of this single-center, retrospective cohort study was to identify whether combination therapy is associated with a lower rate of adverse outcomes for the treatment of Gram negative non-HACEK IE. The primary endpoint was a composite of 60-day all-cause mortality, readmission, or recurrence of bacteremia. Of the 60 patients included, 56.7% met the primary composite outcome, with 20% overall mortality at 60 days. There was no difference in the primary composite outcome of 60-day readmission, infection recurrence or mortality between groups, with 62% of patients in the monotherapy group and 50% of patients in the combination therapy group experiencing the composite outcome (P = 0.36). Despite the high mortality and complicated nature of non-HACEK Gram negative IE, this study showed no difference in 60-day bacteremia recurrence, readmission or mortality among patients treated with combination therapy or monotherapy, suggesting that monotherapy may lead to similar clinical outcomes.

Necrotizing Skin and Soft Tissue Infections Admitted to Intensive Care Unit in Reunion Island: A Retrospective Cohort Study.

This retrospective and single-center study in Reunion Island (Indian Ocean) assessed frequency, mortality, causative pathogens of severe necrotizing skin, and necrotizing skin and soft tissue infections (NSSTIs) admitted in intensive care unit (ICU). Sixty-seven consecutive patients were included from January 2012 to December 2018. Necrotizing skin and soft tissue infection represented 1.06% of total ICU admissions. We estimate the incidence of NSSTI requiring ICU at 1.21/100,000 person/years in Reunion Island. Twenty (30%) patients were receiving nonsteroidal anti-inflammatory drugs (NSAIDs) prior to admission in ICU and 40 (60%) were diagnosed patients with diabetes. Sites of infection were the lower limb in 52 (78%) patients, upper limb in 4 (6%), and perineum in 10 (15%). The surgical treatment was debridement for 40 patients, whereas 11 patients required an amputation. The most commonly isolated microorganisms were Streptococci (42%) and Gram-negative bacteria (22%).The mortality rate was 25.4%. NSAIDs did not influence mortality when interrupted upon admission to ICU.

Fatal Pandoraea nosoerga infection after combined liver-lung transplantation for cystic fibrosis: a recontamination by the pre-transplantation strain.

A 26-year-old girl with a longstanding colonization by Pandoraea nosoerga underwent liver-lung transplantation for cystic fibrosis (CF) in 2018. Her brother also suffering from CF was also colonized by P. nosoerga. Despite appropriate perioperative antibiotic therapy, she had post-transplant bacteremic pneumonia caused by extensively drug-resistant P. nosoerga. Drug repurposing was used to optimize treatment options. The cause of post-transplant contamination was studied by comparative whole-genome sequencing including pre- and post-transplant strains and her brother's strains. Post-transplant contamination appeared to be due to her own pre-transplant strain, emphasizing the urgent need to study and implement effective decontamination protocols before transplantation.

Characterization of antimicrobial-resistant Gram-negative bacteria that cause neonatal sepsis in seven low- and middle-income countries.

Antimicrobial resistance in neonatal sepsis is rising, yet mechanisms of resistance that often spread between species via mobile genetic elements, ultimately limiting treatments in low- and middle-income countries (LMICs), are poorly characterized. The Burden of Antibiotic Resistance in Neonates from Developing Societies (BARNARDS) network was initiated to characterize the cause and burden of antimicrobial resistance in neonatal sepsis for seven LMICs in Africa and South Asia. A total of 36,285 neonates were enrolled in the BARNARDS study between November 2015 and December 2017, of whom 2,483 were diagnosed with culture-confirmed sepsis. Klebsiella pneumoniae (n = 258) was the main cause of neonatal sepsis, with Serratia marcescens (n = 151), Klebsiella michiganensis (n = 117), Escherichia coli (n = 75) and Enterobacter cloacae complex (n = 57) also detected. We present whole-genome sequencing, antimicrobial susceptibility and clinical data for 916 out of 1,038 neonatal sepsis isolates (97 isolates were not recovered from initial isolation at local sites). Enterobacterales (K. pneumoniae, E. coli and E. cloacae) harboured multiple cephalosporin and carbapenem resistance genes. All isolated pathogens were resistant to multiple antibiotic classes, including those used to treat neonatal sepsis. Intraspecies diversity of K. pneumoniae and E. coli indicated that multiple antibiotic-resistant lineages cause neonatal sepsis. Our results will underpin research towards better treatments for neonatal sepsis in LMICs.

Amikacin nebulization for the adjunctive therapy of gram-negative pneumonia in mechanically ventilated patients: a systematic review and meta-analysis of randomized controlled trials.

Treatment of ventilated patients with gram-negative pneumonia (GNP) is often unsuccessful. We aimed to assess the efficacy and safety of nebulized amikacin (NA) as adjunctive therapy to systemic antibiotics in this patient population. PubMed, Embase, China national knowledge infrastructure, Wanfang, and the Cochrane database were searched for randomized controlled trials (RCTs) investigating the effect of NA as adjunctive therapy in ventilated adult patients with GNP. Heterogeneity was explored using subgroup analysis and sensitivity analysis. The Grading of recommendations assessment, development, and evaluation approach was used to assess the certainty of the evidence. Thirteen RCTs with 1733 adults were included. The pooled results showed NA had better microbiologic eradication (RR = 1.51, 95% CI 1.35 to 1.69, P < 0.0001) and improved clinical response (RR = 1.23; 95% CI 1.13 to 1.34; P < 0.0001) when compared with control. Meanwhile, overall mortality, pneumonia associated mortality, duration of mechanical ventilation, length of stay in ICU and change of clinical pneumonia infection scores were similar between NA and control groups. Additionally, NA did not add significant nephrotoxicity while could cause more bronchospasm. The use of NA adjunctive to systemic antibiotics therapy showed better benefits in ventilated patients with GNP. More well-designed RCTs are still needed to confirm our results.

A decade of neonatal sepsis caused by gram-negative bacilli-a retrospective matched cohort study.

This study is to determine the incidence and outcome of neonatal gram-negative bacilli (GNB) sepsis in Stockholm, Sweden, and describe bacterial characteristics. This is a retrospective cohort study. All infants with GNB-sepsis between 2006 and 2016 were included and matched with two control groups, with suspected sepsis and uninfected neonates, respectively. Outcome was death before discharge, risk of death within 5 days after sepsis onset, and morbidity. The resistance pattern from all GNB was collected, and all available isolates were subjected to genome typing. All neonates with GNB-sepsis (n = 107) were included, and the cumulative GNB-sepsis incidence was 0.35/1000 live born. The in-hospital mortality was 30/107 (28%). GNB late-onset sepsis (LOS) was associated with an increase in mortality before discharge compared to uninfected controls (OR = 3.9; CI 1.6-9.4) but not versus suspected sepsis. The suspected LOS cases did not statistically differ significantly from uninfected controls. The case fatality rate (CFR) at 5 days was 5/33 (15%) in GNB early-onset sepsis (EOS) and 25/74 (34%) in GNB-LOS. The adjusted hazard for 5 days CFR was higher in GNB-LOS versus uninfected controls (HR = 3.7; CI 1.2-11.2), but no significant difference was seen in GNB-LOS versus suspected sepsis or in suspected sepsis versus controls. ESBL production was seen in 7/107 (6.5%) of the GNB isolates. GNB-LOS was associated with a higher 5 days CFR and in-hospital mortality compared to uninfected controls but not versus suspect sepsis. The incidence of both GNB-EOS and GNB-LOS was lower than previously reported from comparable high-income settings. The occurrence of antibiotic resistance was low.

Effect on 30-day mortality and duration of hospitalization of empirical antibiotic therapy in CRGNB-infected pneumonia.

BACKGROUND: The objective of this study was to investigate whether unreasonable empirical antibiotic treatment (UEAT) had an impact on 30-day mortality and duration of hospitalization in bacterial pneumonia caused by carbapenem-resistant gram-negative bacteria (CRGNB). METHODS: This was a retrospective cohort study involving CRGNB-infected pneumonia. All CRGNB-infected pneumonia patients received empirical and targeted antibiotic treatment (TAT), and they were divided into reasonable empirical antibiotic treatment (REAT) and UEAT according to whether the empirical antibiotic treatment (EAT) was reasonable. The data of the two groups were compared to analyze their influence on the 30-day mortality and hospitalization time in CRGNB-infected pneumonia patients. Moreover, we also considered other variables that might be relevant and conducted multivariable regression analysis of 30-day mortality and duration of hospitalization in CRGNB-infected pneumonia patients. RESULTS: The study collected 310 CRGNB-infected pneumonia patients, the most common bacterium is Acinetobacter baumannii (211/310 [68%]), the rest were Klebsiella pneumoniae (46/310 [15%]), Pseudomonas aeruginosa and others (53/310 [17%]). Among them, 76/310 (24.5%) patients received REAT. In the analysis of risk factors, dementia, consciousness were risk factors of 30-day mortality, pulmonary disease, hemodynamic support at culture taken day and recent surgery were risk factors for longer hospital stay. The analysis of 30-day mortality showed that UEAT was not associated with 30-day mortality for the 30-day mortality of REAT and UEAT were 9 of 76 (11.84%) and 36 of 234 (15.38%) (P = 0.447), respectively. Meanwhile, there was difference between REAT and UEAT (P = 0.023) in the analysis of EAT on hospitalization time in CRGNB-infected pneumonia patients. CONCLUSIONS: UEAT was not associated with 30-day mortality while was related to duration of hospitalization in CRGNB-infected pneumonia patients, in which Acinetobacter baumanniii accouned for the majority.

Evaluation of the Neonatal Sequential Organ Failure Assessment and Mortality Risk in Preterm Infants With Late-Onset Infection.

Importance: Infection in neonates remains a substantial problem. Advances for this population are hindered by the absence of a consensus definition for sepsis. In adults, the Sequential Organ Failure Assessment (SOFA) operationalizes mortality risk with infection and defines sepsis. The generalizability of the neonatal SOFA (nSOFA) for neonatal late-onset infection-related mortality remains unknown. Objective: To determine the generalizability of the nSOFA for neonatal late-onset infection-related mortality across multiple sites. Design, Setting, and Participants: A multicenter retrospective cohort study was conducted at 7 academic neonatal intensive care units between January 1, 2010, and December 31, 2019. Participants included 653 preterm (<33 weeks) very low-birth-weight infants. Exposures: Late-onset (>72 hours of life) infection including bacteremia, fungemia, or surgical peritonitis. Main Outcomes and Measures: The primary outcome was late-onset infection episode mortality. The nSOFA scores from survivors and nonsurvivors with confirmed late-onset infection were compared at 9 time points (T) preceding and following event onset. Results: In the 653 infants who met inclusion criteria, median gestational age was 25.5 weeks (interquartile range, 24-27 weeks) and median birth weight was 780 g (interquartile range, 638-960 g). A total of 366 infants (56%) were male. Late-onset infection episode mortality occurred in 97 infants (15%). Area under the receiver operating characteristic curves for mortality in the total cohort ranged across study centers from 0.71 to 0.95 (T0 hours), 0.77 to 0.96 (T6 hours), and 0.78 to 0.96 (T12 hours), with utility noted at all centers and in aggregate. Using the maximum nSOFA score at T0 or T6, the area under the receiver operating characteristic curve for mortality was 0.88 (95% CI, 0.84-0.91). Analyses stratified by sex or Gram-stain identification of pathogen class or restricted to infants born at less than 25 weeks' completed gestation did not reduce the association of the nSOFA score with infection-related mortality. Conclusions and Relevance: The nSOFA score was associated with late-onset infection mortality in preterm infants at the time of evaluation both in aggregate and in each center. These findings suggest that the nSOFA may serve as the foundation for a consensus definition of sepsis in this population.

Efficacy of adjunctive nebulized colistin in critically ill patients with nosocomial carbapenem-resistant Gram-negative bacterial pneumonia: a multi-centre observational study.

OBJECTIVES: To investigate the association between adjunctive nebulized colistin and treatment outcomes in critically ill patients with nosocomial carbapenem-resistant Gram-negative bacterial (CR-GNB) pneumonia. METHODS: This retrospective, multi-centre, cohort study included individuals admitted to the intensive care unit with nosocomial pneumonia caused by colistin-susceptible CR-GNB. Enrolled patients were divided into groups with/without nebulized colistin as adjunct to at least one effective intravenous antibiotic. Propensity score matching was performed in the original cohort (model 1) and a time-window bias-adjusted cohort (model 2). The association between adjunctive nebulized colistin and treatment outcomes was analysed. RESULTS: In total, 181 and 326 patients treated with and without nebulized colistin, respectively, were enrolled for analysis. The day 14 clinical failure rate and mortality rate were 41.4% (75/181) versus 46% (150/326), and 14.9% (27/181) versus 21.8% (71/326), respectively. In the propensity score-matching analysis, patients with nebulized colistin had lower day 14 clinical failure rates (model 1: 41% (68/166) versus 54.2% (90/166), p 0.016; model 2: 35.3% (41/116) versus 56.9% (66/116), p 0.001). On multivariate analysis, nebulized colistin was an independent factor associated with fewer day 14 clinical failures (model 1: adjusted odds ratio (aOR) 0.59, 95% CI 0.37-0.92; model 2: aOR 0.37, 95% CI 0.21-0.65). Nebulized colistin was not associated independently with a lower 14-day mortality rate in the time-dependent analysis in both models 1 and 2. CONCLUSIONS: Adjunctive nebulized colistin was associated with lower day 14 clinical failure rate, but not lower 14-day mortality rate, in critically ill patients with nosocomial pneumonia caused by colistin-susceptible CR-GNB.