Gram-negative Late-onset Sepsis Research Articles

Fecal Volatile Metabolomics Predict Gram-Negative Late-Onset Sepsis in Preterm Infants: A Nationwide Case-Control Study.

Early detection of late-onset sepsis (LOS) in preterm infants is crucial since timely treatment initiation is a key prognostic factor. We hypothesized that fecal volatile organic compounds (VOCs), reflecting microbiota composition and function, could serve as a non-invasive biomarker for preclinical pathogen-specific LOS detection. Fecal samples and clinical data of all preterm infants (≤30 weeks' gestation) admitted at nine neonatal intensive care units in the Netherlands and Belgium were collected daily. Samples from one to three days before LOS onset were analyzed by gas chromatography-ion mobility spectrometry (GC-IMS), a technique based on pattern recognition, and gas chromatography-time of flight-mass spectrometry (GC-TOF-MS), to identify unique metabolites. Fecal VOC profiles and metabolites from infants with LOS were compared with matched controls. Samples from 121 LOS infants and 121 matched controls were analyzed using GC-IMS, and from 34 LOS infants and 34 matched controls using GC-TOF-MS. Differences in fecal VOCs were most profound one and two days preceding Escherichia coli LOS (Area Under Curve; p-value: 0.73; p = 0.02, 0.83; p < 0.002, respectively) and two and three days before gram-negative LOS (0.81; p < 0.001, 0.85; p < 0.001, respectively). GC-TOF-MS identified pathogen-specific discriminative metabolites for LOS. This study underlines the potential for VOCs as a non-invasive preclinical diagnostic LOS biomarker.

Gram-negative Late Onset Neonatal Sepsis in a Tertiary Care Center From Central India: A Retrospective Analysis.

Neonatal sepsis has been a major cause of neonatal mortality and morbidity globally. Late onset sepsis is on the rise mostly due to better health care services and improved survival of premature neonates. Gram-negative sepsis has emerged as a major public health problem constituting significant morbidity and mortality. There is limited data on gram-negative late onset sepsis from the central part of India, therefore this study was conducted at a tertiary care center from rural part of India. To determine the clinical profile and outcome among neonates with gram-negative late onset sepsis. It is a retrospective analysis conducted among neonates with gram-negative late onset sepsis at a tertiary care center from central India. All neonates below 28 days of age suspected to have late onset sepsis were enrolled in the study. The data for the period of January 2019 to December 2021 was collected and analyzed using software SPSS version 29. The outcome variables studied were discharge (good outcome) and death (poor outcome). In the present study, overall prevalence of gram-negative late onset sepsis was 4.8%. Respiratory distress (52.2%), seizure (18.9%), jaundice (15.6%), and lethargy (15.6%) were common clinical symptoms among neonates with sepsis. The most common organism isolated was Klebsiella spp. (36.7%) followed by Acinetobacter spp. (31.1%) and E. coli (17.8%). Low gestational age (n = 20 vs n = 7, P = .002) and low birth weight (n = 33 vs n = 4, P = .02) were associated with poor outcomes in neonates with gram negative LOS. The overall mortality rate was found to be 30% among neonates with gram negative sepsis. The prevalence of gram-negative sepsis was found to be 4.8%. Factors associated with poor outcome in gram-negative sepsis were low birth weight, and prematurity. Klebsiella spp. was found to be a common cause of gram-negative LOS, therefore, the empiric antibiotic policy must provide coverage against these micro-organisms.

Safety and efficacy of colistin and fluoroquinolone in neonatal persistent late-onset sepsis

Growing resistance of microorganisms to antibiotics for the treatment of late-onset sepsis (LOS) in premature infants has led physicians to use antibiotics that are not well studied in neonatal populations. We aimed to determine the efficacy and safety of colistin and fluoroquinolone for the treatment of persistent LOS. We retrospectively reviewed infants with gram-negative LOS, who received either colistin or fluoroquinolone therapy, to determine if there was a significant difference in kidney and liver function tests and electrolyte levels before, during, and at the end of the treatment. Infants who received colistin and fluoroquinolone had 17 and 34 positive cultures with gram-negative organisms, respectively. Multi-drug resistant organisms were more common in infants who received colistin than in those who received fluoroquinolone. Microbiological clearance was found to be higher in infants treated with fluoroquinolone than in those treated with colistin. In both the groups, the median levels of kidney and liver function tests and electrolytes showed a significant increase during the treatment. The prescription of colistin and fluoroquinolones should be reserved for cases with no other safe and effective alternatives.

Profound Pathogen-Specific Alterations in Intestinal Microbiota Composition Precede Late-Onset Sepsis in Preterm Infants: A Longitudinal, Multicenter, Case-Control Study.

The role of intestinal microbiota in the pathogenesis of late-onset sepsis (LOS) in preterm infants is largely unexplored but could provide opportunities for microbiota-targeted preventive and therapeutic strategies. We hypothesized that microbiota composition changes before the onset of sepsis, with causative bacteria that are isolated later in blood culture. This multicenter case-control study included preterm infants born under 30 weeks of gestation. Fecal samples collected from the 5 days preceding LOS diagnosis were analyzed using a molecular microbiota detection technique. LOS cases were subdivided into 3 groups: gram-negative, gram-positive, and coagulase-negative Staphylococci (CoNS). Forty LOS cases and 40 matched controls were included. In gram-negative LOS, the causative pathogen could be identified in at least 1 of the fecal samples collected 3 days prior to LOS onset in all cases, whereas in all matched controls, this pathogen was absent (P = .015). The abundance of these pathogens increased from 3 days before clinical onset. In gram-negative and gram-positive LOS (except CoNS) combined, the causative pathogen could be identified in at least 1 fecal sample collected 3 days prior to LOS onset in 92% of the fecal samples, whereas these pathogens were present in 33% of the control samples (P = .004). Overall, LOS (expect CoNS) could be predicted 1 day prior to clinical onset with an area under the curve of 0.78. Profound preclinical microbial alterations underline that gut microbiota is involved in the pathogenesis of LOS and has the potential as an early noninvasive biomarker.

Meropenem vs standard of care for treatment of neonatal late onset sepsis (NeoMero1): A randomised controlled trial.

BackgroundThe early use of broad-spectrum antibiotics remains the cornerstone for the treatment of neonatal late onset sepsis (LOS). However, which antibiotics should be used is still debatable, as relevant studies were conducted more than 20 years ago, recruited in single centres or countries, evaluated antibiotics not in clinical use anymore and had variable inclusion/exclusion criteria and outcome measures. Moreover, antibiotic-resistant bacteria have become a major problem in many countries worldwide. We hypothesized that efficacy of meropenem as a broad-spectrum antibiotic is superior to standard of care regimens (SOC) in empiric treatment of LOS and aimed to compare meropenem to SOC in infants aged <90 days with LOS.Methods and findingsNeoMero-1 was a randomized, open-label, phase III superiority trial conducted in 18 neonatal units in 6 countries. Infants with post-menstrual age (PMA) of ≤44 weeks with positive blood culture and one, or those with negative culture and at least with two predefined clinical and laboratory signs suggestive of LOS, or those with PMA >44 weeks meeting the Goldstein criteria of sepsis, were randomized in a 1:1 ratio to receive meropenem or one of the two SOC regimens (ampicillin+gentamicin or cefotaxime+gentamicin) chosen by each site prior to the start of the study for 8–14 days. The primary outcome was treatment success (survival, no modification of allocated therapy, resolution/improvement of clinical and laboratory markers, no need of additional antibiotics and presumed/confirmed eradication of pathogens) at test-of-cure visit (TOC) in full analysis set. Stool samples were tested at baseline and Day 28 for meropenem-resistant Gram-negative organisms (CRGNO). The primary analysis was performed in all randomised patients and in patients with culture confirmed LOS. Proportions of participants with successful outcome were compared by using a logistic regression model adjusted for the stratification factors. From September 3, 2012 to November 30th 2014, total of 136 patients (instead of planned 275) in each arm were randomized; 140 (52%) were culture positive. Successful outcome at TOC was achieved in 44/136 (32%) in the meropenem arm vs. 31/135 (23%) in the SOC arm (p = 0.087). The respective numbers in patients with positive cultures were 17/63 (27%) vs. 10/77 (13%) (p = 0.022). The main reason of failure was modification of allocated therapy. Treatment emergent adverse events occurred in 72% and serious adverse events in 17% of patients, the Day 28 mortality was 6%. Cumulative acquisition of CRGNO by Day 28 occurred in 4% of patients in the meropenem and 12% in the SOC arm (p = 0.052).ConclusionsWithin this study population, we found no evidence that meropenem was superior to SOC in terms of success at TOC, short term hearing disturbances, safety or mortality were similar in both treatment arms but the study was underpowered to detect the planned effect. Meropenem treatment did not select for colonization with CRGNOs. We suggest that meropenem as broad-spectrum antibiotic should be reserved for neonates who are more likely to have Gram-negative LOS, especially in NICUs where microorganisms producing extended spectrum- and AmpC type beta-lactamases are circulating.

Red cell distribution width as a predictor of late-onset Gram-negative sepsis.

Late-onset sepsis (LOS) remains an important cause of morbidity and mortality in preterm infants. In this study, our aim was to investigate the red-cell distribution width (RDW) levels during a LOS episode, and its association with the type of growing microorganism and mortality. Preterm infants with culture-proven sepsis during their neonatal intensive care unit stay were enrolled. Red-cell distribution width levels were obtained in the first 4h of postnatal life and at the onset of the LOS episode, and compared for these time frames. The study cohort was divided into two groups according to the type of the growing microorganism. The RDW levels were then assessed in intra- and inter-group analyses. Eighty-six infants were included in the final analysis. RDW levels were increased in the study cohort after a LOS attack (P < 0.001). Infants with Gram-negative sepsis showed a significant increase in their RDW levels, but they remained unchanged in infants with Gram-positive sepsis (P < 0.001 and P = 0.4, respectively). An RDW cut-off of >19.50% was related with a sensitivity of 87% and a specificity of 81% for predicting late-onset Gram-negative sepsis (P < 0.001). Logistic regression analysis showed a positive association of RDW with mortality when adjusted for covariants (adjusted odds ratio: 1.40; 95% confidence interval: 1.02-1.80; P = 0.03). Our findings show that RDW levels increased during a LOS episode in preterm infants, which was especially evident in Gram-negative infections. We believe that these findings may be of importance in the early diagnosis and prognosis of LOS in preterm infants.

Gram-negative Late-onset Sepsis in Extremely Low Birth Weight Infants Is Emerging in The Netherlands Despite Quality Improvement Programs and Antibiotic Stewardship!

Late-onset sepsis (LOS) is still an important cause of morbidity and mortality in premature infants. Indwelling devices and lower birth weight (BW) are the most important risk factors. Quality improvement programmes are implemented to reduce incidence of LOS. An increasing number of extremely low BW infants (ELBWs) (≤1000 g) are treated in the Netherlands, including infants with gestational age (GA) 24 weeks since Dutch law changed in 2010. We evaluated the incidence and causative microorganisms of LOS in ELBWs over an 8-year period in 2 Dutch neonatal intensive care units (NICUs). The first LOS episodes of all ELBWs admitted to the NICU of the Wilhelmina Children's Hospital Utrecht and the Isala Hospital Zwolle were included retrospectively from January 2008 to December 2015. LOS was defined as clinical signs of sepsis >72 hours postpartum, combined with a positive blood culture and C-reactive protein of ≥10 mg/L. Two hundred fifty-five out of 923 ELBWs (27.6%) had an episode of LOS, and no decrease in incidence was seen over the years. ELBWs with LOS had lower GA and BW. The percentage of Gram-negative organisms increased from 0% in 2008 to 27% in 2015, mainly in infants with GA <26 weeks. The number of invasive fungal infections decreased to zero. No significant decrease in incidence of LOS in ELBWs was seen, despite the introduction of quality improvement programmes and attention to antibiotic stewardship. Furthermore, an increase in Gram-negative LOS was observed, with an overrepresentation among the growing proportion of the NICU population at the lowest GA and weight. Prevention, including high compliance to hand hygiene policies, may be an impactful intervention.

Outcome of Late-onset Neonatal Sepsis at a Tertiary Hospital in Oman.

ObjectivesWe sought to determine the prevalence, pattern of causative organisms, and mortality of newborns with culture-proven late-onset sepsis (LOS) and to determine and compare the risk factors linked to late-onset gram-positive and late-onset gram-negative sepsis in Sultan Qaboos University Hospital (SQUH).MethodsWe conducted a cross-sectional retrospective study of data obtained between 1 January 2007 and 31 December 2014 (eight years) from infants in the neonatal intensive care unit (NICU) at SQUH. Infants born in SQUH (inborn) and other institutions (outborn) with positive blood cultures were included in the study.ResultsThe total number of live births and admissions during the study period were 26 289 and 3559, respectively. The total number of infants identified with LOS were 125 of whom 69 (55.2%) were gram-positive, 52 (41.6%) were gram-negative, and four (3.2%) were due to Candida species (spp.). The majority of infants (n = 113, 90.4%) were inborn; 69 (55.2%) were males and 56 (44.8%) were females. The prevalence of LOS among inborn admissions was 4.3 per 1000 live births. Most infections occurred in very low birth weight infants (n = 81, 64.8%). Eleven (8.8%) infants died due to gram-negative sepsis. Klebsiella pneumoniae followed by Pseudomonas aeruginosa were the leading cause of death. Maternal intrapartum antibiotics were the only independent risk factor correlating with gram-negative organisms in multivariate analysis (p = 0.003).ConclusionsLOS poses a burden in the NICU, which could be due to the increasing survival of premature babies. The main contributing organisms to LOS are gram-positive bacteria. Klebsiella spp. is a major cause of mortality in LOS. The use of intrapartum antibiotic prophylaxis in mothers might explain the positive correlation of maternal antibiotics as a risk factor with gram-negative infections.

Interleukin-6 serum levels predict surgical intervention in infants with necrotizing enterocolitis

BackgroundSymptoms at suspicion of necrotizing enterocolitis (NEC) are often nonspecific and several biomarkers have been evaluated for their discriminative power to both diagnose and predict the course from NEC suspicion to complicated disease requiring surgical intervention. Thus, we aimed to assess the utility of interleukin-6 (IL-6) to predict surgical intervention in infants suffering from NEC and, furthermore, to discriminate infants with starting NEC or late-onset sepsis (LOS). MethodsIL-6 serum levels at disease onset were retrospectively analyzed in 24 infants suffering from NEC as well as 16 neonates with LOS. ResultsIL-6 serum levels at disease onset were significantly higher in infants suffering from NEC necessitating surgical intervention in the disease course compared to infants with medical NEC (5000 [785–5000] vs. 370 [78–4716] pg/ml, p = 0.0008) as well as gram-positive LOS (5000 [785–5000] vs. 84 [12–269] pg/ml, p = 0.0001). Infants suffering from gram-negative LOS exhibited elevated IL-6 serum levels at disease onset comparable to infants with surgical NEC (5000 [1919–5000] vs. 5000 [785–5000] pg/ml, p = 1.00). ConclusionThe proinflammatory cytokine IL-6 appears to be a promising marker to distinguish surgical NEC from medical NEC at the onset of disease but cannot discriminate between surgical NEC and gram-negative LOS. Level of evidenceII

Optimal infusion rate in antimicrobial therapy explosion of evidence in the last five years.

BackgroundSporadic studies in antimicrobial therapy have evaluated the effects of infusion rates on therapeutic and economic outcomes, and new findings may challenge the regular infusion regimen.MethodsFocusing on studies comparing the outcomes of different infusion regimens, the relevant literature was identified by searching PubMed, Web of Science, and Scopus from January 1, 2013 to March 1, 2018. Papers were finally chosen using a PRISMA flowchart.ResultsAntimicrobials with the superiority of prolonged infusion to standard infusion in terms of efficacy and safety include meropenem, doripenem, imipenem, cefepime, ceftazidime, piperacillin/tazobactam, linezolid, and vancomycin. The strategy of concomitantly reducing total daily dose and prolonging infusion time may cause treatment failure (eg, imipenem). Extended infusion of piperacillin/tazobactam has pharmacoeconomic advantage over standard infusion. Prolonged infusion of voriconazole is inferior to standard infusion because of lower efficacy caused by pharmacokinetic changes. Comparable outcomes following standard infusion and continuous infusion were observed with norvancomycin and nafcillin. Factors determining whether prolonged infusion has a benefit over standard infusion include MIC of bacterial pathogens, bacterial density, diagnosis, disease severity, total daily dose, and renal function.ConclusionTo maximally preserve the effectiveness of current antimicrobials, effective interventions should be implemented to enhance the application of optimal infusion strategies. For reducing nephrotoxicity, prolonged infusion of meropenem is better than conventional infusion in neonates with Gram-negative late-onset sepsis, and continuous infusion of vancomycin is superior to intermittent infusion. For increasing efficacy, prolonged or continuous infusion of time-dependent antimicrobials (eg, meropenem, doripenem, imipenem, cefepime, ceftazidime, piperacillin/tazobactam, linezolid, and vancomycin) is an optimal choice. Nevertheless, such advantages may only be demonstrated in special clinical circumstances and special populations (eg, patients with a sequential organ failure assessment (SOFA) score≥9, respiratory tract infections, urinary or intra-abdominal infections, or infections caused by less susceptible pathogens would benefit from prolonged infusion of piperacillin/tazobactam).

Plasma and CSF pharmacokinetics of meropenem in neonates and young infants: results from the NeoMero studies.

BackgroundSepsis and bacterial meningitis are major causes of mortality and morbidity in neonates and infants. Meropenem, a broad-spectrum antibiotic, is not licensed for use in neonates and infants below 3 months of age and sufficient information on its plasma and CSF disposition and dosing in neonates and infants is lacking.ObjectivesTo determine plasma and CSF pharmacokinetics of meropenem in neonates and young infants and the link between pharmacokinetics and clinical outcomes in babies with late-onset sepsis (LOS).MethodsData were collected in two recently conducted studies, i.e. NeoMero-1 (neonatal LOS) and NeoMero-2 (neonatal meningitis). Optimally timed plasma samples (n = 401) from 167 patients and opportunistic CSF samples (n = 78) from 56 patients were analysed.ResultsA one-compartment model with allometric scaling and fixed maturation gave adequate fit to both plasma and CSF data; the CL and volume (standardized to 70 kg) were 16.7 (95% CI 14.7, 18.9) L/h and 38.6 (95% CI 34.9, 43.4) L, respectively. CSF penetration was low (8%), but rose with increasing CSF protein, with 40% penetration predicted at a protein concentration of 6 g/L. Increased infusion time improved plasma target attainment, but lowered CSF concentrations. For 24 patients with culture-proven Gram-negative LOS, pharmacodynamic target attainment was similar regardless of the test-of-cure visit outcome.ConclusionsSimulations showed that longer infusions increase plasma PTA but decrease CSF PTA. CSF penetration is worsened with long infusions so increasing dose frequency to achieve therapeutic targets should be considered.

Late-onset Neonatal Sepsis-A 10-year Review From North Queensland, Australia.

Late-onset sepsis (LOS) in neonates contributes significantly to both morbidity and mortality. To determine the incidence of LOS, risk factors for disease and the impact on subsequent hospital course, we evaluated a cohort of 6340 neonates admitted to the neonatal intensive care unit and of neonates (3-28 days) admitted from the community between January 2005 and January 2016. This was a retrospective case review of all neonates admitted with suspected LOS who had positive blood culture and/or cerebrospinal fluid cultures, for an organism determined to be a pathogen. Of 6340 neonates who survived beyond 3 days, 2271 (35.8%) had 1 or more blood cultures collected for suspected LOS. Of these, 146 (6.4%) positive blood cultures were thought to represent true bacteremia. The vast majority of infections (73%) were caused by Gram-positive organisms, with coagulase-negative staphylococci accounting for 39.8% of infections. Late-onset neonatal sepsis occurred predominantly in the 24-28-week age group (75.9%) and in neonates who weighed less than 1000 g (73.6%). The incubation time for positive blood cultures for Gram-negative sepsis was less (13 hours) when compared with Gram-positive sepsis (20 hours). Thrombocytopenia, elevated C-reactive protein and chorioamnionitis were consistently associated with late-onset Gram-negative sepsis (P < 0.05). Eight neonates (6%) died secondary to LOS. LOS contributes significantly to mortality and morbidity in neonates and remains a challenge to clinicians. Necessary steps to reduce late-onset neonatal sepsis should be undertaken.

Risk factors and clinical outcomes for carbapenem-resistant Gram-negative late-onset sepsis in a neonatal intensive care unit

Carbapenem-resistant (CR), Gram-negative (GN), late-onset sepsis (LOS) is a serious threat in the neonatal intensive care unit (NICU). To assess the prevalence of CR-GN-LOS in NICU patients and to identify the risk factors and outcomes associated with its acquisition. Neonates with carbapenem-susceptible (CS)-GN-LOS were compared with those with CR-GN-LOS in a two-year observational study. A total of 158 patients had GN-LOS; 100 infants had CS-GN-LOS and 58 infants had CR-GN-LOS. The incidence rate of CR-GN-LOS was 6.5 cases per 1000 patient-days. The most frequent bacterial strain in both groups was Klebsiella pneumoniae. The duration of total parenteral nutrition (TPN) (P=0.006) and prior carbapenem use (P=0.01) were independent risk factors for CR-GN-LOS acquisition. CR-GN-LOS was associated with higher mortality than CS-GN-LOS (P=0.04). Birth weight, small for gestational age, time to start enteral feeding, exclusive formula feeding, previous surgery, previous antifungal use, central venous device before onset, duration of central venous device, and infectious complications were identified as dependent risk factors for overall mortality. However, only male gender (P=0.04) and infectious complications (P < 0.001) were independent risk factors associated with mortality. Infectious complication rates, duration of mechanical ventilation, and length of hospital stay were significantly higher in infants with CR compared to CS-GN-LOS. The duration of TPN and carbapenem use were the independent predictors for CR-GN-LOS acquisition. CR-GN-LOS is associated with higher mortality, infectious complication rates, longer mechanical ventilation, and longer hospital stay. Male gender and infectious complications were the independent risk factors for mortality in neonates with GN-LOS.

Conventional Versus Prolonged Infusion of Meropenem in Neonates With Gram-negative Late-onset Sepsis: A Randomized Controlled Trial.

Gram-negative bacteria are associated with significant morbidity and mortality in preterm and term newborns. Meropenem has widespread efficacy and often allows for monotherapy in this group. Prolonged infusion instead of infusion over 30 minutes has been suggested to result in higher microbiologic efficacy. To compare the clinical and microbiologic efficacy and safety of prolonged infusions versus conventional dosing of meropenem in neonates with Gram-negative late-onset sepsis (GN-LOS). A prospective, randomized clinical trial was conducted in neonates with GN-LOS admitted to neonatal intensive care unit (NICU), Mansoura University Children's Hospital, between August 2013 and June 2015. Patients were randomly assigned to receive either intravenous infusion of meropenem over 4 hours (infusion group) or 30 minutes (conventional group) at a dosing regimen of 20 mg/kg/dose every 8 hours and 40 mg/kg/dose every 8 hours in meningitis and Pseudomonas infection. Clinical and microbiologic success in eradication of infection were the primary outcomes. Neonatal mortality, meropenem-related (MR) duration of mechanical ventilation, MR length of NICU stay, total length of NICU stay, duration of respiratory support (RS), duration of mechanical ventilation, MR duration of inotropes and adverse effects were secondary outcomes. A total of 102 infants (51 in each group) were recruited. The infusion group demonstrated a significantly higher rate of clinical improvement and microbiologic eradication 7 days after starting meropenem therapy compared with the conventional group. Mortality and duration of RS were significantly less in the infusion group compared with conventional group. Acute kidney injury after meropenem treatment was significantly less in the infusion group compared with the conventional group. Prolonged infusion of meropenem in neonates with GN-LOS is associated with higher clinical improvement, microbiologic eradication, less neonatal mortality, shorter duration of RS and less acute kidney injury compared with the conventional strategy.

Postnatal colonization shapes the immunologic development of the neonatal intestinal barrier. (MUC9P.751)

Abstract Microbial colonization of the newborn intestines begins immediately following birth and continues gradually over a period of weeks in both mice and humans. Many preterm infants are unable to secure their intestinal barrier against opportunistic pathogens, resulting in Late-Onset Sepsis (LOS). Here we present a novel murine model of Gram-negative LOS that mimics the natural disease course seen in premies-colonization absent tissue destruction, translocation across the intestines, and bacteremia resulting in sepsis and death. We find that maternal exposure to broad-spectrum Gram-negative (Gentamicin), but not Gram-positive (Vancomycin) antibiotics profoundly affects survival following infection with Klebsiella pneumoniae. Concordantly, neonates from Gentamicin-exposed dams show marked decrease in IL-22 production from Innate Lymphocytes and decreased Tumor Necrosis Factor-alpha (TNF-a) from both CD4+ and CD8+ T cells. These results offer a novel model to study bacterial translocation in the neonatal gut and suggest possible mechanisms through which the intestinal barrier is maintained during the physiologic colonization of the mammalian intestines.

Bacteriological profile and clinical predictors of ESBL neonatal sepsis

Study objective: Bacteriologic profile and risk factors for ESBL sepsis in newborns admitted to a Level III NICU. Methods: This was a retrospective observational study that enrolled newborns admitted to NICU with perinatal risk factors or clinical signs of sepsis and positive blood culture from January 2013 to August 2014. Blood cultures were done by BACTEC and ESBL production was evaluated from double-disc synergy method. Maternal, perinatal and neonatal risk factors were recorded from the case records and computerized information base. Mothers received cephalosporins for PPROM but its use was restricted in newborns for both probable and culture-positive sepsis. Results: Among the infants with sepsis 24% had early-onset sepsis. The incidence of ESBL of early-onset Gram-negative sepsis (EOGNS) was 44.7% (n = 17 of 38) and it was 65% in late-onset Gram-negative sepsis (n = 84 of 129). The predominant ESBL-producing microbe responsible for neonatal sepsis was Klebsiella sp. Among newborns with EOGNS, the risk factors for the production of ESBL were preterm PROM (p = 0.004) and maternal exposure to antibiotics (p = 0.05). Conclusion: ESBL Gram-negative sepsis is a substantial problem in neonatal infections. Maternal exposure to cephalosporins and maternal PPROM are important risk factors for ESBL Gram-negative EOS.

Mucosal surveillance cultures in predicting Gram-negative late-onset sepsis in neonatal intensive care units

This study aimed to examine the spectrum and time course of gut and nasopharyngeal colonization with Gram-negative micro-organisms, and to define the value of surveillance cultures in predicting late-onset sepsis in neonates admitted to neonatal intensive care units. Nasopharyngeal and rectal swabs were collected on admission and twice weekly thereafter in 278 neonates admitted within the first 72h of life with risk factors of early-onset sepsis. Sterile body fluid cultures were obtained on admission and subsequently as clinically indicated. Approximately half of the rectal (693/1250, 55%) and nasopharyngeal (558/1153, 48%) samples but only 6% (32/555) of the sterile fluid samples in 26 patients were culture positive for Gram-negative organisms. In total, 2108 invasive and mucosal culture pairs were analysed. The overall sensitivity, specificity, and positive and negative predictive values of a mucosal sample to predict late-onset sepsis were 27%, 66%, 4% and 94%, respectively. Patients with pre-existing colonization with Klebsiella pneumoniae (P=0.011), Klebsiella oxytoca (P=0.002), Escherichia coli (P=0.003), Stenotrophomonas spp. (P=0.003) and Pseudomonas spp. (P≤0.001) were more likely to develop late-onset sepsis. No such association was found for Acinetobacter baumannii, Serratia spp. or Enterobacter cloacae. In conclusion, routine mucosal cultures are inefficient for the prediction of Gram-negative late-onset sepsis in neonatal intensive care units. However, targeted screening for specific organisms in an outbreak (e.g. Klebsiella spp., E.coli, Stenotrophomonas spp. and Pseudomonas spp.) may offer an opportunity to improve infection control measures and enable timely initiation of appropriate antibiotic therapy.

Risk factors for late onset gram-negative infections: a case–control study

ObjectivesTo determine the incidence, mortality and risk factors for neonatal late onset gram-negative sepsis and meningitis (LOGNS).DesignRetrospective case–control study.SettingTertiary neonatal unit in London.PatientsConsecutive inborn infants with late onset (>48 h...

Risk Factors for Late Onset Gram-Negative Sepsis in Low Birth Weight Infants Hospitalized in the Neonatal Intensive Care Unit

Gram-negative bloodstream infections (BSIs) cause 20-30% of late onset sepsis in neonatal intensive care unit (NICU) patients and have mortality rates of 30-50%. We investigated risk factors for late onset Gram-negative sepsis in very low birth weight (<1500 g) NICU patients. We performed a case-control study as part of a larger 2-year clinical trial that examined the effects of hand hygiene practices on hospital-acquired infections. In this substudy, a case was a very low birth weight infant with a hospital-acquired Gram-negative BSI; control subjects, matched on study site and hand hygiene product, were chosen randomly from the patients who did not have Gram-negative BSIs. Potential risk factors were analyzed by Mantel-Haenszel methods and conditional logistic regression. There were 48 cases of Gram-negative BSI. In multivariate analysis, we found that the following variables were significantly associated with Gram-negative BSI: central venous catheterization duration of >10 days; nasal cannula continuous positive airway pressure use; H2 blocker/proton pump inhibitor use; and gastrointestinal tract pathology. These analyses provide insights into potential strategies to reduce Gram-negative BSIs. Catheters should be removed as possible and H2 blockers/proton pump inhibitors should be used judiciously in NICU patients. The association between nasal cannula continuous positive airway pressure and Gram-negative BSIs requires further investigation. The association of gastrointestinal tract pathology with Gram-negative BSIs identifies a high risk group of neonates who may benefit from enhanced preventative strategies.

Epidemiological, clinical, and microbiological characteristics of late-onset sepsis among very low birth weight infants in Israel: a national survey.

Nosocomial infections are a serious problem among very low birth weight (VLBW) infants. We studied the association between late-onset sepsis (LOS) and mortality and morbidity in VLBW infants. Methods. From a national cohort of 5555 VLBW infants born in Israel during 1995 through 1998, 4829 survived at least 3 days and composed the study population. Maternal, perinatal, or postnatal variables that showed a significant association with LOS in a univariate analysis were tested in a bivariate analysis (adjusted for gestational age). Variables with P </=.1 were then tested by a multiple logistic regression for assessing the net effect of each variable on the risk for LOS. One or more episodes of bloodstream-proven LOS occurred in 1453 infants (30%). Gram-positive and Gram-negative bacteria accounted for 55.4% and 31.2% of microbes, respectively, mainly coagulase-negative Staphylococci and KLEBSIELLA: Compared with those without LOS, infants with LOS had a significantly higher mortality rate (16.9% vs 8.6%). Mortality after Gram-negative LOS (26.2%) and Candida LOS (27.6%) was similar and significantly higher than with Gram-positive LOS (8.7%). Significant independent predictors of LOS were decreasing gestational age, cesarean section, mechanical ventilation, patent ductus arteriosus, necrotizing enterocolitis, and bronchopulmonary dysplasia. LOS occurred in 30% of Israeli VLBW infants. Six strong independent predictors for LOS were identified. Recognition and awareness of the epidemiologic, clinical, and microbiologic characteristics of LOS remain the keystones for management of this nosocomial infection.