Cause Of Late-onset Sepsis Research Articles

Characterisation of neonatal Staphylococcus capitis NRCS-A isolates compared with non NRCS-A Staphylococcus capitis from neonates and adults.

Staphylococcus capitis is a frequent cause of late-onset sepsis in neonates admitted to Neonatal Intensive Care Units (NICU). One clone of S. capitis, NRCS-A has been isolated from NICUs globally although the reasons for the global success of this clone are not well understood.We analysed a collection of S. capitis colonising babies admitted to two NICUs, one in the UK and one in Germany as well as corresponding pathological clinical isolates. Genome analysis identified a population structure of three groups; non-NRCS-A isolates, NRCS-A isolates, and a group of 'proto NRCS-A' - isolates closely related to NRCS-A but not associated with neonatal infection. All bloodstream isolates belonged to the NRCS-A group and were indistinguishable from strains carried on the skin or in the gut. NRCS-A isolates showed increased tolerance to chlorhexidine and antibiotics relative to the other S. capitis as well as enhanced ability to grow at higher pH values. Analysis of the pangenome of 138 isolates identified characteristic nsr and tarJ genes in both the NRCS-A and proto groups. A CRISPR-cas system was only seen in NRCS-A isolates which also showed enrichment of genes for metal acquisition and transport.We found evidence for transmission of S. capitis NRCS-A within NICU, with related isolates shared between babies and multiple acquisitions by some babies. Our data show NRCS-A strains commonly colonise uninfected babies in NICU representing a potential reservoir for potential infection. This work provides more evidence that adaptation to survive in the gut and on skin facilitates spread of NRCS-A, and that metal acquisition and tolerance may be important to the biology of NRCS-A. Understanding how NRCS-A survives in NICUs can help develop infection control procedures against this clone.

The Role of Coagulase-Negative Staphylococci Biofilms on Late-Onset Sepsis: Current Challenges and Emerging Diagnostics and Therapies

Infections are one of the most significant complications of neonates, especially those born preterm, with sepsis as one of the principal causes of mortality. Coagulase-negative staphylococci (CoNS), a group of staphylococcal species that naturally inhabit healthy human skin and mucosa, are the most common cause of late-onset sepsis, especially in preterms. One of the risk factors for the development of CoNS infections is the presence of implanted biomedical devices, which are frequently used for medications and/or nutrient delivery, as they serve as a scaffold for biofilm formation. The major concerns related to CoNS infections have to do with the increasing resistance to multiple antibiotics observed among this bacterial group and biofilm cells' increased tolerance to antibiotics. As such, the treatment of CoNS biofilm-associated infections with antibiotics is increasingly challenging and considering that antibiotics remain the primary form of treatment, this issue will likely persist in upcoming years. For that reason, the development of innovative and efficient therapeutic measures is of utmost importance. This narrative review assesses the current challenges and emerging diagnostic tools and therapies for the treatment of CoNS biofilm-associated infections, with a special focus on late-onset sepsis.

Improved Genomic Prediction of Staphylococcus epidermidis Isolation Sources with a Novel Polygenic Score.

Staphylococcus epidermidis infections can be challenging to diagnose due to the species frequent contamination of clinical specimens and indolent course of infection. Nevertheless, S. epidermidis is the major cause of late-onset sepsis among premature infants and of intravascular infection in all age groups. Prior work has shown that bacterial virulence factors, antimicrobial resistances, and strains have up to 80% in-sample accuracy to distinguish hospital from community sources, but are unable to distinguish true bacteremia from blood culture contamination. Here, a phylogeny-informed genome-wide association study of 88 isolates was used to estimate effect sizes of particular genomic variants for isolation sources. A "polygenic score" was calculated for each isolate as the summed effect sizes of its repertoire of genomic variants. Predictive models of isolation sources based on polygenic scores were tested with in-samples and out-samples from prior studies of different patient populations. Polygenic scores from accessory genes (AGs) distinguished hospital from community sources with the highest accuracy to date, up to 98% for in-samples and 65% to 91% for various out-samples, whereas scores from single nucleotide polymorphisms (SNPs) had lower accuracy. Scores from AGs and SNPs achieved the highest in-sample accuracy to date, up to 76%, in distinguishing infection from contaminant sources within a hospital. Model training and testing data sets with more similar population structures resulted in more accurate predictions. This study reports the first use of a polygenic score for predicting a complex bacterial phenotype and shows the potential of this approach for enhancing S. epidermidis diagnosis.

Molecular Epidemiology of Neonatal-Associated Staphylococcus haemolyticus Reveals Endemic Outbreak.

Staphylococcus haemolyticus is a major cause of late-onset sepsis in neonates, and endemic clones are often multidrug-resistant. The bacteria can also act as a genetic reservoir for more pathogenic bacteria. Molecular epidemiology is important in understanding bacterial pathogenicity and preventing infection. To describe the molecular epidemiology of S. haemolyticus isolated from neonatal blood cultures at a Swedish neonatal intensive care unit (NICU) over 4 decades, including antibiotic resistance genes (ARGs), virulence factors, and comparison to international isolates. Isolates were whole-genome sequenced, and single nucleotide polymorphisms in the core genome were used to map the relatedness. The occurrence of previously described ARGs and virulence genes were investigated. Disc diffusion and gradient tests were used to determine phenotypic resistance. The results revealed a clonal outbreak of S. haemolyticus at this NICU during the 1990s. Multidrug resistance was present in 28 (82%) of all isolates and concomitant resistance to aminoglycoside and methicillin occurred in 27 (79%). No isolates were vancomycin resistant. Genes encoding ARGs and virulence factors occurred frequently. The isolates in the outbreak were more homogenous in their genotypic and phenotypic patterns. Genotypic and phenotypic resistance combinations were consistent. Pathogenic traits previously described in S. haemolyticus occurred frequently in the present isolates, perhaps due to the hospital selection pressure resulting in epidemiological success. The clonal outbreak revealed by this study emphasizes the importance of adhering to hygiene procedures in order to prevent future endemic outbreaks. IMPORTANCE This study investigated the relatedness of Staphylococcus haemolyticus isolated from neonatal blood and revealed a clonal outbreak in the 1990s at a Swedish neonatal intensive care unit. The outbreak clone has earlier been isolated in Japan and Norway. Virulence and antibiotic resistance genes previously associated with clinical S. haemolyticus were frequently occuring in the present study as well. The majority of the isolates were multidrug-resistant. These traits should be considered important for S. haemolyticus epidemiological success and are probably caused by the hospital selection pressure. Thus, this study emphasizes the importance of restrictive antibiotic use and following the hygiene procedures, to prevent further antibiotic resistance spread and future endemic outbreaks.

P367 Candida sepsis in neonates a neglected pathogen: study from neonatal intensive care unit tertiary care hospital

Poster session 3, September 23, 2022, 12:30 PM - 1:30 PM IntroductionSignificance of Candida species in neonatal intensive care units (NICU) is increasingly being recognized. It is the third most common cause of late-onset sepsis in NICU patients and accounts for 9 to 13% of bloodstream infections (BSI) in neonates. Although Candida albicans has historically been the most frequently isolated species, recently non-albicans Candida (NAC) have emerged as an important opportunistic pathogen, notably Candida tropicalis, C. parapsilosis, C. krusei, C. glabrata, and C auris. This changing trend and the increasing use of azoles agents is now a matter of concern due to the emerging resistance of the non-albicans species to azoles.AimTo evaluate the Candida sepsis in neonates from neonatal intensive care units from a tertiary care hospital.Material and MethodsA cross-sectional study was conducted in the Department of Microbiology, University College of Medical Sciences and Guru Teg Bahadur Hospital, East Delhi, India, during the period of July 2021 to December 2021. Overall, 30 suspected Candida sepsis patients from neonatal intensive care units were enrolled in the present study. The Candida spp. Isolated was identified as per standard mycological techniques. Preliminary identification was done by colony morphology on SDA, chromogenic media (Hichrome, Himedia Pvt. Ltd.), grown at 45°C, germ tube test, chlamydospore formation, and was confirmed by carbohydrate fermentation and assimilation tests. Antifungal susceptibility testing (AFST) was performed for Fluconazole (25 μg), and amphotericin B (AMB, 100 units) using the disc diffusion method on Muller-Hinton agar supplemented with 2% glucose and methylene blue (5 mg/ml). Zone diameters were interpreted as per the approved Clinical Laboratory Standards (CLSI-M44-A) guidelines. Quality control for AFST was performed using C. albicans-ATCC 90028 and C. parapsilosis-ATCC 22019.Statistical analysisThe statistical analysis was done using Statistical Package for Social Sciences (SPSS) version. The P-value ˂0.05 were considered as statistically significant.ResultOut of 30 Candida species from suspected septicemia neonates, non-albicans Candida (NAC) species accounted for (87%) compared to C. albicans (13.4%). Candida tropicalis was predominant at 9 (30%) followed by C. glabrata 8 (27%), C.parapsilosis 4 (13.3%), and C. krusei 3(10%), Pichia species (4.2%), and C.auris (3.4%). Antifungal sensitivity of the NAC isolates demonstrated >85% resistance to fluconazole amongst C. glabrata, C. parapsilosis, though amphotericin B had 100% sensitivity in all Candida species. The risk factor for candidemia as observed in our study were low birth weight 26(87%), use of broad-spectrum antibiotics 25 (83.4%), presence of an orogastric tube 18 (60%), and total parental nutrition 9 (30%) were significantly associated statistically (P <.05, paired t-test). The overall mortality amongst these neonates was 16.6%.ConclusionFungal BSI has emerged as an important cause of morbidity and mortality in neonates. Reporting of fungal bloodstream infections and the spectrum of species involved are essential measures in neonatal intensive care units in order to implement appropriate preventive and therapeutic strategies.

Clinical Risk Factors Associated With Late-Onset Invasive Group B Streptococcal Disease: Systematic Review and Meta-Analyses.

BackgroundGroup B streptococcal (GBS) infection remains one of the most significant causes of late-onset sepsis and meningitis (LOGBS) among young infants. However, transmission routes and risk factors for LOGBS are not yet fully understood.MethodsWe conducted systematic reviews on clinical risk factors previously reported in the literature (prematurity, low birth weight [<2500 g], antenatal colonization, multiple-gestation pregnancy, maternal age <20 years, male infant sex, intrapartum fever, prolonged rupture of membranes) and meta-analyses to determine pooled estimates of risk.ResultsWe included 27 articles, reporting 5315 cases. Prematurity (odds ratio [OR] 5.66; 95% confidence interval [CI]: 4.43–7.22), low birth weight (OR 6.73; 95% CI: 4.68–9.67), maternal colonization (2.67; [2.07–3.45]), and multiple-gestation pregnancies (OR 8.01; 95% CI: 5.19–12.38) were associated with an increased risk of LOGBS.ConclusionsPrematurity/low birth weight and maternal colonization are major risk factors for LOGBS. Future GBS vaccine studies should try to establish the optimal time for vaccination during pregnancy to protect preterm infants.

Association of Antibiotic Duration and Outcomes among NICU Infants with Invasive Staphylococcus aureus Infections

Background:Staphylococcus aureus is the second-leading cause of late-onset sepsis among infants in US neonatal intensive care units (NICUs). Management of S. aureus bacteremia and meningitis in infants varies widely due to the lack of standardized guidelines. We examined the association between initial antibiotic duration and recurrent S. aureus infection or death among NICU infants with S. aureus bacteremia and/or meningitis. Methods: We conducted a retrospective cohort study of infants in Pediatrix Medical Group NICUs from 1997 to 2018 with first episode of S. aureus bacteremia and/or meningitis, identified as having at least 1 blood or cerebrospinal fluid (CSF) culture growing only S. aureus at any point during their NICU stay. Excluded infants were those not started on antistaphylococcal therapy within 2 days of positive culture, those with had endocarditis or osteomyelitis, or those who died or were discharged during or up to 1 day after antibiotic cessation. Antibiotic cessation was defined as last day of antibiotic given if followed by at least 3 days without antibiotics. Multivariable logistic regression was used to analyze the association between antibiotic duration categorized as &lt;14 or ≥14 days) and recurrent SA infection (within 12 weeks of antibiotic cessation, prior to hospital discharge), or death (within 7 days of antibiotic cessation and at discharge). Results: Of 4,086 infants included, 3,991 (98%) had S. aureus bacteremia only and 95 (2%) had meningitis ± bacteremia. Of those with bacteremia only, 2,017 (50.5%), and 17 (18%) of those with meningitis received &lt;14 days antibiotics (Figure 1). Longer antibiotic duration was associated with lower gestational age, methicillin-resistance, severe illness and bacteremia duration of ≥4 days (Table 1). There was a significant association between &lt;14 days antibiotics and recurrent infection (p = 0.04) and 7-day mortality (p = 0.02) in the meningitis cohort. Infants with SA bacteremia who received ≥14 days antibiotics had reduced odds of recurrent SA infection (OR 0.24, 95% CI 0.18-0.32) and death (OR 0.33, 95% CI 0.25-0.44), adjusting for post-natal age, gestational age, sex, methicillin-resistance, severe illness and duration of bacteremia (Table 2). Conclusions: In the largest study thus far examining antibiotic duration among hospitalized infants with S. aureus bacteremia and/or meningitis, ≥14 days antibiotics was associated with decreased odds of recurrent infection or death. Further studies are needed to define the optimal treatment duration and identify clinical factors distinguishing infants able to safely receive a shorter antibiotic duration.Funding: NoDisclosures: None

Incidence and microbiological characteristics of neonatal late onset sepsis in a neonatal intensive care unit in Peru

ObjectivesOur study aimed to determine the incidence of late onset sepsis and the most frequent microorganisms causing it in the neonatal unit at Hospital Cayetano Heredia in Lima, Peru. MethodsDescriptive and retrospective study. We reviewed all positive blood cultures and cultures of cerebrospinal fluid drawn from inborn patients beyond 72 h of life, admitted to the neonatal unit from January 2015 to December 2019. ResultsThe incidence of late onset sepsis was 7.4% of admitted patients and 10.04 per 1000 live births. During our study period, 234 episodes of late onset sepsis occurred in 204 patients. The incidence was higher in very low birth weight infants, reaching 36.2% and even higher in extremely low birth weight infants (40.7%). Coagulase-negative Staphylococcus and then Klebsiella spp. were the most frequent causative microorganisms. The most frequent cause of late onset sepsis in very low birth weight infants was gram-negative bacteria (Klebsiella spp., was the most frequent causative microorganism). ConclusionsLate onset neonatal sepsis is prevalent in our neonatal unit. It is important to know which are the most prevalent causative microorganisms to be able to choose adequate antibiotic coverage and to design strategies to prevent infection.

Updated Guidance: Prevention and Management of Perinatal Group B Streptococcus Infection.

Group B Streptococcus (GBS) remains the most common cause of neonatal early-onset sepsis among term infants and a major cause of late-onset sepsis among both term and preterm infants. The American Academy of Pediatrics and the American College of Obstetricians and Gynecologists published separate but aligned guidelines in 2019 and 2020 for the prevention and management of perinatal GBS disease. Together, these replace prior consensus guidelines provided by the Centers for Disease Control and Prevention. Maternal intrapartum antibiotic prophylaxis based on antenatal screening for GBS colonization remains the primary recommended approach to prevent perinatal GBS disease, though the optimal window for screening is changed to 36 0/7 to 37 6/7 weeks of gestation rather than beginning at 35 0/7 weeks' gestation. Penicillin, ampicillin, or cefazolin are recommended for prophylaxis, with clindamycin and vancomycin reserved for cases of significant maternal penicillin allergy. Pregnant women with a history of penicillin allergy are now recommended to undergo skin testing, because confirmation of or delabeling from a penicillin allergy can provide both short- and long-term health benefits. Aligned with the American Academy of Pediatrics recommendations for evaluating newborns for all causes of early-onset sepsis, separate consideration should be given to infants born at less than 35 weeks' and more than or equal to 35 weeks' gestation when performing GBS risk assessment. Empiric antibiotics are recommended for infants at high risk for GBS early-onset disease. Although intrapartum antibiotic prophylaxis is effective in preventing GBS early-onset disease, currently there is no approach for the prevention of GBS late-onset disease.

Hyperpigmentation as a cutaneous manifestation of fungal sepsis in neonates: Case series report.

With improved and prolonged survival of very and extremely low birth weight infants, invasive fungal infection has emerged as an important concern in the neonatal intensive care units. Candidiasis is the third leading cause of late onset sepsis in these neonates and is associated with 20-30% mortality. Extreme prematurity, central venous catheters, prolonged antibiotic exposure, parenteral nutrition are important risk factors. Various forms of cutaneous manifestations of candidiasis have been described ranging from local diaper dermatitis and oral thrush to widespread erosive and ulcerative lesions with extensive crusting in invasive fungal dermatitis. We report a series of four cases with cutaneous hyperpigmentation as manifestation of systemic candidiasis.

Clinical features and outcomes of community‐acquired late‐onset sepsis: Focusing on group B Streptococcus and Escherichia coli

Group B Streptococcus (GBS) and Escherichia coli are leading causes of late-onset sepsis (LOS) and bacterial meningitis in neonates and infants. This study aimed to describe clinical characteristics and outcomes of community-acquired (CA) LOS caused by GBS and E.coli. A retrospective observational study was performed in three university hospitals in Korea. All infants aged <90days who were diagnosed with GBS or Ecoli CA-LOS from 2011 to 2017 were enrolled. Data on the clinical characteristics and outcomes of GBS and E.coli CA-LOS were compared. Forty GBS and 43 E.coli CA-LOS cases were identified, which mostly (82/83) included term or near-term infants. Meningitis was identified in 54.1% of GBS CA-LOS cases and in 30.3% of E.coli CA-LOS cases, and 88.4% of E.coli CA-LOS cases involved urosepsis. Ten percent each of GBS and non-uropathogenic E.coli (non-UPEC) meningitis cases and all uropathogenic E. coli (UPEC) meningitis cases were diagnosed by pleocytosis without bacterial growth in the cerebrospinal fluid (CSF). Patients with non-culture-proven meningitis had lower CSF pleocytosis and protein levels and higher CSF/serum glucose ratios than patients with culture-proven meningitis (P<0.05 for all). One patient died of CA-LOS, which was accompanied by meningitis with extended-spectrum β-lactamase-producing non-UPEC. Neurological complications developed in 22.5% of GBS CA-LOS cases and in 2.3% of E.coli CA-LOS cases. Neurological complications were frequently observed in GBS CA-LOS cases, although no mortality was observed. Escherichia coli CA-LOS generally developed as urosepsis, which caused non-culture-proven meningitis and had a favorable outcome.

Management of Infants at Risk for Group B Streptococcal Disease.

Group B streptococcal (GBS) infection remains the most common cause of neonatal early-onset sepsis and a significant cause of late-onset sepsis among young infants. Administration of intrapartum antibiotic prophylaxis is the only currently available effective strategy for the prevention of perinatal GBS early-onset disease, and there is no effective approach for the prevention of late-onset disease. The American Academy of Pediatrics joins with the American College of Obstetricians and Gynecologists to reaffirm the use of universal antenatal microbiologic-based testing for the detection of maternal GBS colonization to facilitate appropriate administration of intrapartum antibiotic prophylaxis. The purpose of this clinical report is to provide neonatal clinicians with updated information regarding the epidemiology of GBS disease as well current recommendations for the evaluation of newborn infants at risk for GBS disease and for treatment of those with confirmed GBS infection. This clinical report is endorsed by the American College of Obstetricians and Gynecologists (ACOG), July 2019, and should be construed as ACOG clinical guidance.

Genetic Relatedness of Staphylococcus haemolyticus in Gut and Skin of Preterm Neonates and Breast Milk of Their Mothers.

Staphylococcus haemolyticus is a common colonizer and cause of late-onset sepsis (LOS) in preterm neonates. By describing genetic relatedness, we aimed to determine whether mother's breast milk (BM) is a source of S. haemolyticus colonizing neonatal gut and skin and/or causing LOS. S. haemolyticus was isolated from stool and skin swabs of 49 BM-fed preterm neonates admitted to neonatal intensive care unit, 20 healthy BM-fed term neonates and BM of mothers once a week and typed by multilocus variable number tandem repeat analysis and multilocus sequence typing. Virulence-related genes were determined by polymerase chain reaction. Compared with term neonates, S. haemolyticus colonized more commonly gut (35% vs. 89.9%; P < 0.001) and skin (50% vs. 91.8%; P < 0.001) of preterm neonates and mothers' BM (15% vs. 38.8%). Isolates from preterm compared with term neonates and their mothers carried more commonly the mecA gene (83.5% vs. 5.4%; P < 0.001) and IS256 (52.4% vs. 2.7%; P < 0.001) and belonged to clonal complex 29 (89.1% vs. 63%; P = 0.014). Only 7 (14.3%) preterm and 3 (15%) term neonates were colonized in gut or on skin with multilocus variable number tandem repeat analysis types indistinguishable from those in BM. Most frequent multilocus variable number tandem repeat analysis types belonged to sequence type 3 or 42, comprised 71.1%-78.4% of isolates from preterm neonates/mothers and caused all 7 LOS episodes. LOS-causing strain colonized the gut of 4/7 and the skin of 5/7 neonates, but not BM, before onset of LOS. S. haemolyticus colonizing gut and skin or causing LOS in preterm neonates rarely originate from BM but are mecA-positive strains adapted to hospital environment.

Systemic Candida infection in preterm babies: Experience from a tertiary care hospital of North India

Background: Neonatal fungal infection is an important cause of late-onset sepsis with very high mortality. The incidence is progressively increasing due to a marked improvement in the survival of low-birth weight neonates. Materials and Methods: This was a 2-year observational study. Very low-birth weight (VLBW) and extremely low-birth weight (ELBW) with suspected fungal sepsis were enrolled. All suspected neonates were evaluated for possible Candida infection. Complete clinicodemographic and laboratory profile was noted from the study participants. The main outcome measure was hospital incidence, clinical profile, and the frequency of end-organ involvement. Results: During the study, 304 ELBW and VLBW neonates were screened for invasive fungal sepsis. Sixty-four neonates were found positive for invasive Candida sepsis making the incidence of 11.6%. Majority of patients developed worsening of respiratory distress and shock. Necrotizing enterocolitis (NEC) was seen in 10 patients and disseminated intravascular coagulation (DIC) in nine patients. Nearly 7.8% had cerebrospinal fluid culture positive for Candida. Renal abscess was seen in two patients. Endohpthalmitis and endocarditis each were observed in one patient. The mortality rate in our study group was 55%. Conclusion: We found 11.9% incidence of invasive fungal incidence. Majority of neonates developed worsening of respiratory distress, shock, NEC, DIC, and thrombocytopenia. End-organ damage was noticed in 14% of patients. Mortality was around 55% in our cohort.

Analysis of late-onset neonatal sepsis cases in a level three neonatal intensive care unit.

OBJECTIVE:Newborns in neonatal intensive care units (NICUs) are at high risk for developing nosocomial infections (NIs), which may result in morbidity and mortality. In this study, we aimed to ascertain the bacteriological profiles and their antimicrobial susceptibility patterns in NIs.METHODS:We conducted a cross-sectional study in the NICU. Late-onset sepsis (LOS) cases confirmed with blood cultures were evaluated retrospectively. Laboratory parameters, demographics, and clinical data were collected and analyzed from hospital records retrospectively.RESULTS:Of the 1210 infants in the NICU, 76 (6.3%) had LOS. A total of 86 episodes of LOS were documented; in 10 infants, two pathogens were identified. The mean gestational age (GA) of the infants with LOS was 33.2±4.8 weeks (23 to 42 weeks). Gram-positive cocci (GPC) caused most of the LOS episodes (65.8%, 50/76), with coagulase-negative Staphylococcus (CoNS) as the most common cause of LOS (50%, 38/76). Gram-negative rod species (GNRs) accounted for 32.9% (25/76) of the LOS cases, and fungi accounted for 1.3% (1/76). The mortality rates for GNR and GPC were 17.9% and 6.4%, respectively (p>0.05). The mean CRP and conjugated bilirubin levels for the GPC and GNR groups were 37.5 vs. 29.5 mg/dl and 0.7 vs 1.5 mg/dl, respectively (p>0.05). GNRs had a 20–25% ceftriaxone resistance. Two (4%) GPC species were resistant to linezolid, while all were susceptible to vancomycin. All of the GNRs were susceptible to carbapenems.CONCLUSION:These results underscore the recent emergence of CoNS in NICUs. LOS due to GNRs seems to display higher C-reactive protein and conjugated bilirubin values than those due to GPC. Clinical monitoring of NIs and bacterial resistance profiles are required in all NICUs.

Urinary tract infection is common in VLBW infants

Determine the significance of urinary tract infection (UTI) as a cause of late onset sepsis (LOS) in very low birth weight (VLBW) infants in the Neonatal Intensive Care Unit (NICU). Analysis of blood, cerebrospinal fluid and urine culture results in VLBW infants >72-h old, admitted to the Georgetown University Hospital NICU between 2005 and 2015. Of 527 VLBW infants, 297 (56.4%) underwent 911 evaluations for LOS; only one-third included urine cultures. UTI was diagnosed in 8.5% of VLBW infants (range 2-15.9%) and in 13.8% of infants weighing < 1000 g at birth. Gram-negative infections predominated. Concomitant blood cultures were negative in 96% of infants. UTI was more common than bloodstream infection by 2015. UTI is a significant cause of infection in VLBW infants. Urine culture should be included in all LOS evaluations in order to facilitate accurate diagnosis and appropriate antibiotic therapy.

Morbidity and mortality of coagulase-negative staphylococcal sepsis in very-low-birth-weight infants.

Coagulase-negative staphylococci (CoNS) are the most common cause of late-onset sepsis in the neonatal intensive care unit (NICU) and usually require vancomycin treatment. Our objective was to determine whether CoNS are associated with neonatal morbidity and mortality. This was a retrospective cohort study of very-low-birth-weight (VLBW,≤1500g) infants from 1989 to 2015. Exclusion criteria were major congenital anomaly or death within 72h. CoNS was considered a pathogen if recovered from≥2 cultures, or 1 culture if treated for≥5days and signs of sepsis were present. Logistic regression was used to examine factors associated with morbidity and mortality. Of 2242 VLBW infants, 285 (12.7%) had late-onset sepsis. CoNS (125, 44%), Staphylococcus aureus (52, 18%), and Escherichia coli (36, 13%) were the most commonly recovered organisms. In multivariate analysis, CoNS sepsis was not associated with mortality [OR 0.6 (95% CI 0.2-2.6)), but sepsis with other organisms was [OR 4.5 (95% CI 2.6-8.0)]. CoNS sepsis was associated with longer hospitalization but not risk for bronchopulmonary dysplasia, intraventricular hemorrhage, or retinopathy of prematurity. CoNS sepsis was not associated with mortality or morbidities other than length of stay. These findings support vancomycin-reduction strategies in the NICU.

Antibiotics at the time of removal of central venous catheter to reduce morbidity and mortality in newborn infants.

Late-onset sepsis is associated with increased rates of mortality and morbidity in newborn infants, in addition to poorer long-term developmental outcomes and increased length of stay and hospital costs. Central line-associated blood stream infection (CLABSI) is the most common cause of late-onset sepsis in hospitalised infants, and prevention of CLABSI is a key objective in neonatal care. Increased frequency of CLABSI around the time of removal of central venous catheters (CVCs) has been reported, and use of antibiotics at the time of removal may reduce the incidence and impact of late-onset sepsis in vulnerable newborn infants. To determine the efficacy and safety of giving antibiotics at the time of removal of a central venous catheter (CVC) for reduction of morbidity and mortality in newborn infants, in particular effects on late-onset sepsis. We used the standard search strategy of the Cochrane Neonatal Review Group without language restriction to search the Cochrane Central Register of Controlled Trials (CENTRAL; 2017, Issue 3), MEDLINE via PubMed (1966 to 6 April 2017), Embase (1980 to 6 April 2017), and the Cumulative Index to Nursing and Allied Health Literature (CINAHL) (1982 to 6 April 2017). We also searched clinical trials databases, conference proceedings, and reference lists of retrieved articles for randomised controlled trials and quasi-randomised trials. Randomised, quasi-randomised, and cluster-randomised trials considering use of any antibiotic or combination of antibiotics at the time of CVC removal in newborn infants compared with placebo, no antibiotics, or another antibiotic or combination of antibiotics. We extracted data using standard methods of the Cochrane Neonatal Review Group. Two review authors independently selected, assessed the quality of, and extracted data from the included study. Only one randomised controlled trial was eligible for inclusion in this analysis. Forty-four of a total of 88 infants received two doses of cephazolin at the time of removal of CVC compared with no antibiotics at the time of removal of CVC in the control group. No infant in the intervention group developed late-onset sepsis after CVC removal compared with five of 44 (11%) in the control group (risk ratio (RR) 0.09, 95% confidence interval (CI) 0.01 to 1.60). Cephazolin given at the time of removal of CVC did not statistically significantly alter late-onset sepsis rates and led to no significant differences in any of the prespecified outcomes. Review authors judged the study to be of low quality because of high risk of bias and imprecision. Randomised controlled trials have provided inadequate evidence for assessment of the efficacy or safety of antibiotics given at the time of CVC removal. The single identified trial was underpowered to address this question. Future research should be directed towards targeting use of antibiotics upon removal of CVC for those at greatest risk of complications from CVC removal-related CLABSI. Researchers should include safety data such as impact upon antibiotic use and resistance patterns. This investigation would best occur as part of a bundle of quality improvement care interventions provided by neonatal networks.

Candida parapsilosis Protects Premature Intestinal Epithelial Cells from Invasion and Damage by Candida albicans.

Candida is a leading cause of late-onset sepsis in premature infants and is thought to invade the host via immature or damaged epithelial barriers. We previously showed that the hyphal form of Candida albicans invades and causes damage to premature intestinal epithelial cells (pIECs), whereas the non-hyphal Candida parapsilosis, also a fungal pathogen of neonates, has less invasion and damage abilities. In this study, we investigated the potential for C. parapsilosis to modulate pathogenic interactions of C. albicans with the premature intestine. While a mixed infection with two fungal pathogens may be expected to result in additive or synergistic damage to pIECs, we instead found that C. parapsilosis was able to protect pIECs from invasion and damage by C. albicans. C. albicans-induced pIEC damage was reduced to a similar extent by multiple different C. parapsilosis strains, but strains differed in their ability to inhibit C. albicans invasion of pIECs, with the inhibitory activity correlating with their adhesiveness for C. albicans and epithelial cells. C. parapsilosis cell-free culture fractions were also able to significantly reduce C. albicans adhesion and damage to pIECs. Furthermore, coadministration of C. parapsilosis cell-free fractions with C. albicans was associated with decreased infection and mortality in zebrafish. These results indicate that C. parapsilosis is able to reduce invasion, damage, and virulence functions of C. albicans. Additionally, the results with cellular and cell-free fractions of yeast cultures suggest that inhibition of pathogenic interactions between C. albicans and host cells by C. parapsilosis occurs via secreted molecules as well as by physical contact with the C. parapsilosis cell surface. We propose that non-invasive commensals can be used to inhibit virulence features of pathogens and deserve further study as a non-pharmacological strategy to protect the fragile epithelial barriers of premature infants.

Treatment Options for Persistent Coagulase Negative Staphylococcal Bacteremia in Neonates.

Coagulase-negative staphylococci (CoNS) are the leading cause of late-onset sepsis in neonatal intensive-care units (NICUs). Despite adequate therapeutic levels and in vivo susceptibility, vancomycin is not always adequate in clearing CoNS bacteremias and other theurapeutic regimens are warranted especially when dealing with persistent CoNS bacteremias. Retrospective analysis of neonates with persistent CoNS bacteremias in a tertiary NICU in two study periods (January 2006 to December 2007 and January 2011 to December 2012). Demographics, clinical characteristics and antibiotics used were recorded. We also performed a literature review on the treatment options for persistent CoNS bacteremia. Out of the 1485 admissions during the 4 years, 121 (8,1%) neonates developed CoNS bacteremia and 42 of them (34.7%) were persistent. The most common CoNS species was S.epidermidis (91%). Apart from the shorter mean duration of bacteremia (p = 0.003), during the second part of the study, no other differences were observed between the two study periods. Ten (23.8%) neonates were treated with vancomycin monotherapy. In 23 (54.7%) neonates, rifampicin was added to vancomycin. Linezolid was given to seven neonates (16.6%), whereas daptomycin was given to two neonates (4.7%). No differences were found when we compared the characteristics of neonates treated with different antibiotics. All neonates tolerated treatment well. Our literature review revealed 16 relevant studies, the majority of which are small case series. The addition of rifampicin, linezolid and daptomycin in neonates with persistent CoNS bacteremia can provide useful therapeutic alternatives. Further studies are required to bring more insight into the field.