Clinical and microbiological characteristics of bloodstream infection caused by Klebsiella pneumoniae harboring rmpA in Japanese adults.

We investigated the clinical features of bloodstream infections (BSIs) caused by Klebsiella pneumoniae harboring rmpA and molecular characteristics of the bacteria. We retrospectively investigated adult patients with K. pneumoniae BSI from January 2010 to March 2021 at Nagasaki University Hospital. A matched case-control study in a 1:3 ratio was conducted to clarify the clinical and bacterial characteristics of BSI caused by rmpA-positive K. pneumoniae compared with those caused by rmpA-negative isolates. Antimicrobial susceptibility testing and multilocus sequence typing (MLST) were performed for rmpA-positive isolates. The rmpA was detected in 36 (13.4%) of the 268 isolates. Of these 36 isolates, 31 (86.1%) harbored iucA and 35 (97.2%) each possessed peg-344 and iroB; capsular types were identified as K1 in 9 (25.0%) and K2 in 10 isolates (27.8%). Contrarily, of the 108 rmpA-negative isolates, which were matched for case-control studies, 5 isolates (4.6%) harbored iucA and 1 (0.9%) each possessed peg-344 and iroB; 2 (1.9%) and 3 isolates (2.8%) had K1 and K2 capsular types, respectively. Among the rmpA-positive isolates, ST23/K1 (eight isolates) was the most frequent, followed by ST412/non-K1/K2 (seven isolates), ST86/K2 (five isolates), and ST268/non-K1/K2 (four isolates). In a multivariate analysis using clinical factors, liver abscess positively correlated with rmpA-positive isolates, whereas biliary tract infection and use of anticancer drugs negatively correlated with rmpA-positive isolates in patients with K. pneumoniae BSI. Considering the correlation between rmpA-positive isolates and clinical features, rmpA can be used as a marker for understanding the pathophysiology of K. pneumoniae BSI.

Sympathetic nerves control bacterial clearance.

A neural reflex mediated by the splanchnic sympathetic nerves regulates systemic inflammation in negative feedback fashion, but its consequences for host responses to live infection are unknown. To test this, conscious instrumented sheep were infected intravenously with live E. coli bacteria and followed for 48 h. A month previously, animals had undergone either bilateral splanchnic nerve section or a sham operation. As established for rodents, sheep with cut splanchnic nerves mounted a stronger systemic inflammatory response: higher blood levels of tumor necrosis factor alpha and interleukin-6 but lower levels of the anti-inflammatory cytokine interleukin-10, compared with sham-operated animals. Sequential blood cultures revealed that most sham-operated sheep maintained high circulating levels of live E. coli throughout the 48-h study period, while all sheep without splanchnic nerves rapidly cleared their bacteraemia and recovered clinically. The sympathetic inflammatory reflex evidently has a profound influence on the clearance of systemic bacterial infection.

Staphylococcus aureus Bacteremia: Contemporary Management.

Staphylococcus aureus bacteremia (SAB) is a serious cause of bloodstream infection associated with significant morbidity and mortality. Complications include deep-seated foci of infection including infective endocarditis, device-associated infection, osteoarticular metastases, pleuropulmonary involvement, and recurrent infection. With the 30-day all-cause mortality being around 20%, a collaborative effort of early Infectious Diseases (ID) consultation and Antimicrobial Stewardship Program (ASP) involvement will show improved SAB outcomes and therapy optimization.1.

Nocardia bacteremia: A single-center retrospective review and a systematic review of the literature.

OBJECTIVES: Nocardia bacteremia is a rare but severe disease associated with high mortality. This systematic review is the largest and most comprehensive review performed over the past 20 years. METHODS: A single-center retrospective review of Nocardia bacteremia was performed using hospital microbiology records from January 1, 2010 to December 31, 2017. A systematic literature review was also performed to identify cases of Nocardia bacteremia described in the NCBI PubMed database in English between January 1, 1999 and December 31, 2018. RESULTS: Four new cases of Nocardia bacteremia are described. The systematic review identified 134 cases with sufficient information available for analysis. Of the total 138 cases, the median age was 58 years (interquartile range (IQR) 44-69 years) and 70% were male. Eighty-one percent were immunocompromised (corticosteroid use (49%), hematological malignancy (20%), solid organ transplant (20%), solid organ malignancy (19%), and hematopoietic stem cell transplantation (15%)) and 29% had endovascular devices. Pulmonary infection was the most common concurrent site of clinical disease (67%). The median incubation time to the detection of Nocardia bacteremia was 4 days (IQR 3-6 days). Blood cultures were the only positive microbiological specimen in 38% of cases. The median total duration of treatment was 75 days (IQR 25-182 days). Thirty-day all-cause mortality was 28% and overall all-cause mortality was 40%. CONCLUSIONS: Nocardia bacteremia is most frequently identified in immunocompromised patients and those with intravascular devices. Although rare, it represents a serious infection with high associated overall mortality.

Risk factors for bacteremia in children with febrile neutropenia

Background/aim: Bacteremia remains an important cause of morbidity and mortality during febrile neutropenia (FN) episodes. We aimed to define the risk factors for bacteremia in febrile neutropenic children with hemato-oncological malignancies. Materials and methods: The records of 150 patients aged ≤18 years who developed FN in hematology and oncology clinics were retrospectively evaluated. Patients with bacteremia were compared to patients with negative blood cultures. Results: The mean age of the patients was 7.5 ± 4.8 years. Leukemia was more prevalent than solid tumors (61.3% vs. 38.7%). Bacteremia was present in 23.3% of the patients. Coagulase-negative staphylococci were the most frequently isolated microorganism. Leukopenia, severe neutropenia, positive peripheral blood and central line cultures during the previous 3 months, presence of a central line, previous FN episode(s), hypotension, tachycardia, and tachypnea were found to be risk factors for bacteremia. Positive central line cultures during the previous 3 months and presence of previous FN episode(s) were shown to increase bacteremia risk by 2.4-fold and 2.5-fold, respectively. Conclusion: Presence of a bacterial growth in central line cultures during the previous 3 months and presence of any previous FN episode(s) were shown to increase bacteremia risk by 2.4-fold and 2.5-fold, respectively. These factors can predict bacteremia in children with FN.

Predictive value of the kinetics of procalcitonin and C-reactive protein for early clinical stability in patients with bloodstream infections due to Gram-negative bacteria.

OBJECTIVE: To investigate whether the magnitude of the change in procalcitonin (PCT) and C-reactive protein (CRP) levels between day 1 and day 2 after the blood culture date is associated with early clinical stability (ECS) on day 3 in patients with bacteremia due to Gram-negative bacteria (GNB). MATERIALS/METHODS: A prospective cohort study carried out in a 950-bed tertiary hospital in Spain between March 2013 and May 2014. Patients with GNB bacteremia were included. Changes in PCT and CRP kinetics from day 1 to day 2 (∆%PCT, ∆%CRP) were expressed as percentage of decline in blood levels. Logistic regression was used to identify predictors of ECS. Classification and regression tree analysis was performed to identify breakpoints. The discriminatory power of ∆%CRP and ∆%PCT as predictors of ECS was assessed by the area under the ROC (AUROC). RESULTS: 71 patients were included, and 53 (74.56%) reached ECS. Multivariate analyses showed that SOFA score on day 1, ∆%PCT, and ∆%CRP were associated with ECS after controlling for confounders. ∆%PCT ≥ 30% (decline) and ∆%CRP ≥ 10% (decline) predicted ECS only among patients with SOFA≤3 on day 1 (n = 54; 43 reached ECS). In these patients, the AUROCs for the prediction of ECS were 0.96 (95% CI: 0.90-1) for ∆%CRP and 0.96 (95% CI: 0.90-1) for ∆%PCT, respectively. CONCLUSIONS: In the subgroup of patients with a SOFA score on day 1 ≤3, a ≥30% decline in PCT or a ≥10% decline in CRP between day 1 and day 2 was a very good predictor of ECS (which in turn was associated with a lower 30-day mortality and a greater clinical cure on day 14). Patients who do not achieve this decrease may need more intensive workup. In this subgroup (with a SOFA on day 1 ≤3), CRP may be preferred due to its lower cost.

Cerebral Abscess Associated With Odontogenic Bacteremias, Hypoxemia, and Iron Loading in Immunocompetent Patients With Right-to-Left Shunting Through Pulmonary Arteriovenous Malformations.

Background: Cerebral abscess is a recognized complication of pulmonary arteriovenous malformations (PAVMs) that allow systemic venous blood to bypass the pulmonary capillary bed through anatomic right-to-left shunts. Broader implications and mechanisms remain poorly explored. Methods: Between June 2005 and December 2016, at a single institution, 445 consecutive adult patients with computed tomography-confirmed PAVMs (including 403 [90.5%] with hereditary hemorrhagic telangiectasia) were recruited to a prospective series. Multivariate logistic regression was performed and detailed periabscess histories were evaluated to identify potential associations with cerebral abscess. Rates were compared to an earlier nonoverlapping series. Results: Thirty-seven of the 445 (8.3%) patients experienced a cerebral abscess at a median age of 50 years (range, 19-76 years). The rate adjusted for ascertainment bias was 27 of 435 (6.2%). Twenty-nine of 37 (78.4%) patients with abscess had no PAVM diagnosis prior to their abscess, a rate unchanged from earlier UK series. Twenty-one of 37 (56.7%) suffered residual neurological deficits (most commonly memory/cognition impairment), hemiparesis, and visual defects. Isolation of periodontal microbes, and precipitating dental and other interventional events, emphasized potential sources of endovascular inoculations. In multivariate logistic regression, cerebral abscess was associated with low oxygen saturation (indicating greater right-to-left shunting); higher transferrin iron saturation index; intravenous iron use for anemia (adjusted odds ratio, 5.4 [95% confidence interval, 1.4-21.1]); male sex; and venous thromboemboli. There were no relationships with anatomic attributes of PAVMs, or red cell indices often increased due to secondary polycythemia. Conclusions: Greater appreciation of the risk of cerebral abscess in undiagnosed PAVMs is required. Lower oxygen saturation and intravenous iron may be modifiable risk factors.

Clinical Characteristics of Methicillin-resistant Coagulase-negative Staphylococcal Bacteremia in a Tertiary Hospital.

Objective Coagulase-negative staphylococci are among the most frequently isolated microorganisms in blood cultures. The aim of this study was to assess [1] the clinical characteristics of methicillin-resistant, coagulase-negative staphylococci bacteremia and [2] the susceptibility of the isolated bacteria to glycopeptides. Methods We retrospectively reviewed the medical records of 70 patients from whom methicillin-resistant coagulase-negative staphylococci had been isolated at Osaka City University Hospital between January 2010 and December 2013. We evaluated the patients' background, severity and prognosis of the disease, and the susceptibility of the isolated methicillin-resistant coagulase-negative staphylococci to glycopeptides. Results Out of the 70 patients tested, 28 (40.0%) had leukemia, and 36 (51.4%) had been treated for febrile neutropenia. Infection with Staphylococcus epidermidis accounted for 78.6% of patients. Thirty-nine cases (55.7%) were related to intravascular catheters, and 39 (55.7%) were treated using teicoplanin as a first-line therapy. The 30-day mortality rate was 4.3%. Regarding susceptibility, 20% of all isolates were non-susceptible to teicoplanin. According to multivariate analyses, it was observed that premedication using glycopeptides was independently associated with teicoplanin non-susceptibility (p=0.03; hazard ratio = 5.64; 95% confidence interval, 1.16-26.76). Conclusion Our results suggest that clinicians must use glycopeptides appropriately to prevent the development of further antibiotic resistance in methicillin-resistant coagulase-negative staphylococci.

Spinal Infections Among Patients With Long-Term Central Venous Catheters for Home Parenteral Nutrition.

Spinal infections are a rare yet serious metastatic complication of bacteremia among patients with long-term central venous catheters (CVCs) for which clinicians must remain vigilant. We performed a retrospective review of all cases of spinal infection occurring in the context of a CVC for long-term parenteral nutrition (PN) managed in our department between January 2010 and October 2013, a cohort of 310 patients over this time period. Six patients were identified (mean age, 65 years; 5 male). One hundred percent of patients presented with spinal pain (5/6 cervical, 1/6 thoracic). Organisms were cultured from the CVC in 5 of 6 patients. In all cases, the white blood cell count was normal, and in 5 of 6, C-reactive protein was normal. All diagnoses were confirmed on magnetic resonance imaging (MRI), and in 3 of 6 cases, an MRI was repeated (on the advice of neurosurgical colleagues) to confirm resolution of changes after a period of antimicrobial therapy. There was no clear correlation between duration of PN or number of days following CVC insertion and onset of infection. The CVC was replaced in 4 of 6 patients at the time of diagnosis, delayed removal in 1 of 6, and salvaged in the remaining case. Although rare, a high index of suspicion is needed in patients receiving long-term PN who present with spinal pain. Peripheral inflammatory markers may not be elevated. MRI should be performed and patients should be treated with antibiotics alongside involvement of local microbiology and neurosurgical teams. Multidisciplinary discussion on CVC salvage in these cases is important, especially in cases of challenging vascular anatomy.

Bacteremia and Deep Vein Thrombosis in an Infant.

BACKGROUND: Deep vein thrombosis (DVT) is rare in infancy. In pediatric populations, thrombosis occurs most frequently in hospitalized children and those with central venous catheters. The presence of a DVT in the general pediatric population indicates a hypercoagulable state and requires rapid diagnosis and treatment of both the thrombosis and the underlying process. CASE REPORT: A previously healthy 6-month-old male was brought to the emergency department by his family with a chief complaint of left leg swelling. Duplex ultrasonography in the emergency department revealed multiple DVTs in the leg vasculature. The patient was treated with anticoagulation and antibiotic therapy in the emergency department and admitted. Blood cultures revealed the subsequent growth of methicillin-resistant Staphylococcus aureus (MRSA). WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: While rare in infants, new-onset swelling in an extremity may be caused by thrombosis and be the initial symptom of an underlying hypercoagulable state. Duplex ultrasonography is a relatively benign test that can be readily performed in most emergency departments, and it allows physicians to rule out thrombosis. When present, DVT in the general pediatric population can indicate a critical illness, such as malignancy or infection, and requires rapid treatment and admission to a pediatric service for management.

Safety and efficacy of hematopoietic stem cells mobilization in patients with multiple sclerosis.

INTRODUCTION: Multiple sclerosis (MS) is a T-cell-mediated chronic inflammatory disorder of the central nervous system. Several agents have been approved for the treatment of MS; however, their efficacy is limited and short term. Autologous hematopoietic stem cell (HSC) transplantation may remain an encouraging option for some MS patients who failed prior conventional treatment. Objective To assess the safety and effectiveness of HSCs mobilization in patients with MS. MATERIAL AND METHODS: Thirty-nine patients (20 females and 19 males) with relapsing-remitting MS at median age of 40 years (range: 25-63) were included in this study. As a stem cell mobilization, they received either granulocyte colony-stimulating factor (G-CSF) alone (10 µg/kg s.c. daily; n = 1) or cyclophosphamide (CY; 2.0 g/m(2) i.v. on days 1-2) followed by G-CSF (n = 38). RESULTS: The median number of mobilized HSCs per kg was 6.32 × 10(6) (range: 2.64-26.3 × 10(6)). One apheresis was sufficient for collection of HSCs in 30 out of 39 MS patients (77%). Two aphereses were required for seven patients, three for one and four for one (17, 3, and 3%; respectively). Side effects of HSCs mobilization have been reported for eight patients (30%) and they were following: Staphylococcus epidermidis bacteremia (n = 1), fever of unknown origin (n = 3), diarrhea (n = 3), and headache (n = 1). CONCLUSIONS: Mobilization using CY and/or G-CSF resulted in effective mobilization in all MS patients. This procedure was found to be safe. No fatal outcome has been reported.

Changes in Gut and Plasma Microbiome following Exercise Challenge in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS).

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a disease characterized by intense and debilitating fatigue not due to physical activity that has persisted for at least 6 months, post-exertional malaise, unrefreshing sleep, and accompanied by a number of secondary symptoms, including sore throat, memory and concentration impairment, headache, and muscle/joint pain. In patients with post-exertional malaise, significant worsening of symptoms occurs following physical exertion and exercise challenge serves as a useful method for identifying biomarkers for exertion intolerance. Evidence suggests that intestinal dysbiosis and systemic responses to gut microorganisms may play a role in the symptomology of ME/CFS. As such, we hypothesized that post-exertion worsening of ME/CFS symptoms could be due to increased bacterial translocation from the intestine into the systemic circulation. To test this hypothesis, we collected symptom reports and blood and stool samples from ten clinically characterized ME/CFS patients and ten matched healthy controls before and 15 minutes, 48 hours, and 72 hours after a maximal exercise challenge. Microbiomes of blood and stool samples were examined. Stool sample microbiomes differed between ME/CFS patients and healthy controls in the abundance of several major bacterial phyla. Following maximal exercise challenge, there was an increase in relative abundance of 6 of the 9 major bacterial phyla/genera in ME/CFS patients from baseline to 72 hours post-exercise compared to only 2 of the 9 phyla/genera in controls (p = 0.005). There was also a significant difference in clearance of specific bacterial phyla from blood following exercise with high levels of bacterial sequences maintained at 72 hours post-exercise in ME/CFS patients versus clearance in the controls. These results provide evidence for a systemic effect of an altered gut microbiome in ME/CFS patients compared to controls. Upon exercise challenge, there were significant changes in the abundance of major bacterial phyla in the gut in ME/CFS patients not observed in healthy controls. In addition, compared to controls clearance of bacteria from the blood was delayed in ME/CFS patients following exercise. These findings suggest a role for an altered gut microbiome and increased bacterial translocation following exercise in ME/CFS patients that may account for the profound post-exertional malaise experienced by ME/CFS patients.

Skin microcirculatory changes reflect early the circulatory deterioration in a fulminant sepsis model in the pig

PURPOSE: In the pathophysiology of sepsis tissue perfusion dysfunction is a crucial driving force. Thus the early recognition is highly important. Concerning the early hours of bacteremia, and the systemic inflammatory response reaction leading to sepsis we aimed to investigate the micro- and macrocirculatory changes. METHODS: In 20 juvenile Hungahib pigs were anesthetized and the femoral artery and external jugular vein were prepared unilaterally and cannulated. For assisted ventilation tracheostomy was performed. In Sepsis group (n=11) live E. coli was intravenously administered (increasing concentration, 9.5x10∧6 in 3h). In Control group (n=9) bacteria-free saline was administered at the same volume. Modified shock index (MSI), core and skin temperature, and skin microcirculation (laser Doppler) were measured before inducing bacteremia then hourly for 4h. RESULTS: In Control group parameters were stable, while six animals in the Sepsis group died before the 4th hour. Core and skin temperature did not show significant alterations. In Sepsis group microcirculation showed a large impairment already by the 1st hour, while in MSI only by the 3rd hour. CONCLUSION: During bacteremia and the early phase of sepsis microcirculatory impairment can be detected soon, even hours before the deterioration in hemodynamic parameters in this porcine model. .

Clinical features and risk factors for development of Bacillus bacteremia among adult patients with cancer: a case-control study.

PURPOSE: Bacillus species have been frequently reported in recent decades as true pathogens among cancer patients. The purpose of this study was to evaluate the clinical features and risk factors of Bacillus bacteremia among adult patients with cancer. METHODS: A case-control study was performed to identify the risk factors of Bacillus bacteremia among adult patients with cancer at a 1,950-bed tertiary care university hospital. Electronic medical records were reviewed for individuals who were diagnosed with Bacillus bacteremia during the period of January 1995 through December 2012. Each case was matched to two controls with cancer and non-Bacillus bacteremia. Logistic regression model was used to identify independent risk factors for Bacillus bacteremia development. RESULTS: A total of 86 patients with Bacillus bacteremia were included and compared with 172 control patients. The presence of a central venous catheter and use of extended-spectrum cephalosporin within 1 month were identified to be independent risk factors for the development of Bacillus bacteremia. Hospital stays longer than 14 days, a history of hematopoietic stem cell transplantation, and prior use of glycopeptides had a negative association. CONCLUSIONS: The presence of a central venous catheter and prior use of extended-spectrum cephalosporin within 1 month were independent risk factors for the development of Bacillus bacteremia in adult cancer patients.

Disseminated nocardiosis during systemic steroid therapy for the prevention of esophageal stricture after endoscopic submucosal dissection.

An 85-year-old man underwent endoscopic submucosal dissection for a large superficial esophageal epithelial neoplasm, which required removal of 95% of the circumference of the esophageal mucosa. Steroids were given orally to prevent esophageal stricture starting on day 3 postoperatively. In the 6th week of steroid treatment, he developed high fever without other symptoms. Chest computed tomography revealed a nodular lesion in the lung. Sputum sample showed Gram-positive, branching, filamentous bacteria, and a diagnosis of nocardiosis was suspected. Brain magnetic resonance imaging revealed multiple focal lesions which indicated dissemination of nocardiosis. Trimethoprim-sulfamethoxazole was immediately started, which led to the disappearance of pulmonary and cerebral nocardiosis with alleviation of fever. Recently, oral steroid treatment has been widely used for the prevention of esophageal stricture. However, the present case indicates the risk of life-threatening infection and the importance of close monitoring of this treatment.

Influence of laparoscopy vs. laparotomy on bacterial translocation and systemic inflammatory responses in a porcine model with peritonitis.

BACKGROUND: This study aimed to compare the effects of laparoscopy vs. laparotomy on bacterial translocation and immunologic responses in a porcine model with peritonitis caused by small bowel injuries (SBIs). METHODS: Pigs with SBIs were first established, assigned into either the laparoscopy group or the laparotomy group, and then received surgical intervention. During 72 hours (72 hr) observation period, blood, and tissues of different organs were obtained for bacterial cultures; endotoxin and peripheral leukocyte were determined; serum levels of IL-6, TNF-α, and CRP were measured. RESULTS: Blood cultures confirmed systemic bacteremia in all animals and the endotoxin level was comparable between groups at 24 hr after surgery. However, two days later, positive bacteremia was only detected in four pigs following laparoscopy and five following laparotomy. Eight and four pigs during laparoscopy (seven and six pigs during laparotomy) had translocated bacteria in mesenteric lymph nodes (MLN) and liver. The 72 hr later, bacteria in MLN, liver, lung, and kidney was found in 2, 1, 2, and 0 pig after laparoscopy, respectively (3, 2, 2, and 1 pig after laparotomy). The peripheral blood monocytes (PBMC) counts remained at a much lower level after laparoscopy than after laparotomy. Serum IL-6, TNF-α, and CRP increased notably after both procedures when compared to preoperative levels. However, significantly faster and lower regression of IL-6, TNF-α, and CRP were observed in the laparoscopy group. CONCLUSION: Compared with laparotomy, laparoscopy does not result in increased bacterial translocation, but decrease IL-6, TNF-α, and CRP release.

Rhodococcus bacteremia in cancer patients is mostly catheter related and associated with biofilm formation.

Rhodococcus is an emerging cause of opportunistic infection in immunocompromised patients, most commonly causing cavitary pneumonia. It has rarely been reported as a cause of isolated bacteremia. However, the relationship between bacteremia and central venous catheter is unknown. Between 2002 and 2010, the characteristics and outcomes of seventeen cancer patients with Rhodococcus bacteremia and indwelling central venous catheters were evaluated. Rhodococcus bacteremias were for the most part (94%) central line-associated bloodstream infection (CLABSI). Most of the bacteremia isolates were Rhodococcus equi (82%). Rhodococcus isolates formed heavy microbial biofilm on the surface of polyurethane catheters, which was reduced completely or partially by antimicrobial lock solution. All CLABSI patients had successful response to catheter removal and antimicrobial therapy. Rhodococcus species should be added to the list of biofilm forming organisms in immunocompromised hosts and most of the Rhodococcus bacteremias in cancer patients are central line associated.

Cytokine screening identifies NICU patients with Gram-negative bacteremia.

INTRODUCTION: Biomarkers and physiomarkers may be useful adjunct tests for sepsis detection in neonatal intensive care unit (NICU) patients. We studied whether measuring plasma cytokines at the time of suspected sepsis could identify patients with bacteremia in centers in which patients were undergoing continuous physiomarker screening using a heart rate characteristics (HRC) index monitor. RESULTS: Six cytokines were higher in Gram-negative bacteremia (GNB) than in Gram-positive bacteremia or candidemia (GPBC). A cytokine score using thresholds for granulocyte colony-stimulating factor (G-CSF), interleukin (IL)-6, IL-8, and tumor necrosis factor (TNF)-α had 100% sensitivity and 69% positive predictive value (PPV) for GNB. A single cytokine marker, IL-6 < 130 pg/ml, had 100% sensitivity and 52% PPV for sepsis ruled out (SRO). The average HRC index was abnormal in this cohort of patients with clinical suspicion of sepsis and did not discriminate between the final sepsis designations. DISCUSSION: In summary, in NICU patients with suspected late-onset sepsis, plasma cytokines can identify those with SRO and those with GNB, potentially aiding in decisions regarding therapy. METHODS: Seven cytokines were measured in 226 plasma samples from patients >3 d old with sepsis suspected based on clinical signs, abnormal HRC index, or both. Cases were classified as SRO, clinical sepsis (CS), GPBC, or GNB.