Coagulase-negative Staphylococcal Sepsis Research Articles

The relevance of coagulase-negative Staphylococcus isolates in blood culture in the context of a tertiary neonatal unit from East India

Background: Coagulase-negative Staphylococcus (CoNS) are known commensals and often contaminate neonatal blood cultures. Their unique ability to form biofilms, however, helps them evade immune mechanisms and antibiotics and cause neonatal sepsis (NS) in hospitalized neonates. True or probable Coagulase-negative Staphylococcus blood stream infection (CoNS BSI) must be differentiated from contaminants so that antibiotics are used judiciously and hospital stay is minimized. Aims and Objectives: The primary objective of the study was to estimate the proportion of NS and contaminants among CoNS-positive blood cultures in the index neonatal unit and the host and health-care variables associated with CoNS BSI. The secondary objective was to estimate the susceptibility of CoNS isolates to antibiotics used. Materials and Methods: This was a retrospective study from digital records, from January 2018 to December 2022. Results: 25% of CoNS isolates were associated with NS (health-care infections) and 75% were contaminants. Over 90% of CoNS BSI was associated with central lines (CLs) and prolonged hospital stay. All isolates were resistant to oxacillin while resistance to gentamicin rose annually to over 68%. Susceptibility to linezolid and vancomycin was present, but a few strains were resistant to them. Conclusion: CoNS were an important cause of NS in the index hospital. Prolonged hospital stays and CLs were associated with increased incidence of CoNS sepsis and must be minimized where possible. Antibiotic resistance was high, and reserve drugs could also become ineffective.

Using population pharmacokinetics to optimize initial vancomycin dosing guidelines for neonates to treat sepsis caused by coagulase-negative staphylococcus.

Vancomycin dosing tailored for newborns is challenging due to the significant influence of maturation and organ function on pharmacokinetics. Population pharmacokinetic (popPK) models can be used to improve target attainment in neonates. The primary objective was to derive and evaluate a popPK model of intravenous vancomycin for neonates. Second, the predictive performance of this popPK model was compared with published popPK models. This is a retrospective cohort study of neonates admitted to the neonatal intensive care unit receiving intravenous vancomycin. A popPK model was derived with 70% of the dataset using a nonlinear mixed effects modeling method. The predictive performance of the current popPK model was validated and compared with 22 published popPK models using the remaining 30% of the dataset. Monte Carlo simulations (MCS) were performed to derive optimal dosing regimens to treat neonatal sepsis caused by coagulase-negative staphylococci (CoNS). Among 655 vancomycin courses from 448 neonates, 78% of vancomycin trough concentrations were outside target range (10-15 mg/L) for central nervous system infections and 43% were outside target range (5-12 mg/L) for other infections using the institution's vancomycin dosing. A one-compartment model best described the observed data with a mean clearance of 0.11 ± 0.03 L/kg/h and volume of distribution (V) of 1.02 ± 0.08 L/kg. Body weight (WT), postmenstrual age (PMA), and serum creatinine (SCr) were significant covariates associated with clearance (p < 0.001) and body WT was a significant covariate associated with V (p = 0.009). Our study's popPK model has similar or better accuracy and precision than other published models. MCS-derived vancomycin doses from the validated model achieved >90% target attainment for a steady state through target range of 10-15 mg/L in the majority of PMA and SCr categories (78%) to treat CoNS sepsis. A vancomycin dosing guideline derived from a validated popPK model in neonates with CoNS sepsis is recommended to improve target attainment.

Glucose supply and glycolysis inhibition shape the clinical fate of Staphylococcus epidermidis-infected preterm newborns.

Preterm infants are susceptible to bloodstream infection by coagulase-negative staphylococci (CONS) that can lead to sepsis. Glucose-rich parenteral nutrition is commonly used to support the infants' growth and energy expenditure but may exceed endogenous regulation during infection, causing dysregulated immune response and clinical deterioration. Using a preterm piglet model of neonatal CONS sepsis induced by Staphylococcus epidermidis (S. epidermidis) infection, we demonstrate the delicate interplay between immunity and glucose metabolism to regulate the host infection response. Circulating glucose levels, glycolysis, and inflammatory response to infection are closely connected across the states of tolerance, resistance, and immunoparalysis. Furthermore, high parenteral glucose provision during infection induces hyperglycemia, elevated glycolysis, and inflammation, leading to metabolic acidosis and sepsis, whereas glucose-restricted individuals are clinically unaffected with increased gluconeogenesis to maintain moderate hypoglycemia. Finally, standard glucose supply maintaining normoglycemia or pharmacological glycolysis inhibition enhances bacterial clearance and dampens inflammation but fails to prevent sepsis. Our results uncover how blood glucose and glycolysis control circulating immune responses, in turn determining the clinical fate of preterm infants infected with CONS. Our findings suggest further refinements of the current practice of parenteral glucose supply for preterm infants during infection.

Persistent Coagulase-Negative Staphylococcal Bacteremia in Neonates: Clinical, Microbiological Characteristics and Changes within a Decade.

Atypical outbreaks of persistent coagulase-negative staphylococci (CoNS) bacteremias, defined as three or more consecutive positive blood cultures with the same CoNS species, at least 48 h apart, have been reported in neonatal intensive-care units (NICUs). Our aim was to describe the profile of these cases in our NICU over a two-year period with the objective of assessing possible changes within a decade. Demographics, clinical and microbiological data were recorded for all CoNS bacteremias in our tertiary NICU during 2016–2017 and compared with the results of the same study in 2006–2007. Fifty-six cases of CoNS sepsis were recorded. Fourteen (25%) of them were persistent. There were no significant differences in demographic and clinical characteristics between cases with persistent vs. non-persistent bacteremia. Staphylococcus epidermidis was the most common species. In logistic regression analysis, biofilm production (β = 2.464, p = 0.04) was the most significant determinant for the development of persistent CoNS bacteremia. Our isolates were less likely to produce biofilm and carry ica operon as compared to those of 2006–2007. The cases of persistent CoNS sepsis have decreased within a decade, which could be attributed to the implementation of intensive infection control practices. Biofilm production remains the most important risk factor.

The Use of Daptomycin in the Treatment of Persistent Coagulase-Negative Staphylococcal Sepsis in Premature Infants: A Case Series.

Daptomycin is a lipopeptide antibiotic with rapid bactericidal activity against Gram-positive bacteria. Reports regarding the use of daptomycin in infants are still limited. Thus, the objective of this report is to describe the safety and efficacy of daptomycin in premature infants with persistent coagulase-negative staphylococci (CoNS) infection. This was a retrospective chart review of 10 premature infants with persistent CoNS infection who received daptomycin therapy between January 2018 and September 2019. Four patients had endocarditis and 1 had bacterial meningitis and infectious endocarditis. The other 5 patients had persistent CoNS bacteraemia only. Daptomycin treatment was successful for 5 patients. The others died owing to multiple factors such as prematurity, sepsis, and chronic lung disease. Adverse drug reactions, including elevation of creatine phosphokinase and/or hepatotoxicity, were noted in 4 patients. Large and randomized studies are necessary to ensure daptomycin's safety and efficacy for the treatment of infants with persistent sepsis caused by Gram-positive bacteria.

Neonatal and Neurodevelopmental Outcomes Following Linezolid for Coagulase-negative Staphylococcal Infection: Real World Evidence.

Coagulase-negative staphylococci (CoNS) frequently causes late-onset sepsis in preterm infants. Vancomycin is the first-line therapy, but the emergence of reduced vancomycin-susceptibility strains has resulted in linezolid use, of which long-term safety in preterm infants is unknown. Evaluate the association between linezolid exposure and neurodevelopmental impairment (NDI) or death at 18-21 months of corrected age, in preterm infants with CoNS sepsis. Multicentric retrospective cohort study comparing long-term outcomes of preterm infants exposed to linezolid versus other antistaphylococcal antimicrobials. We included infants ≤28 weeks' gestational age (GA), with CoNS sepsis, admitted between January 2011 and June 2015 in 3 level-3 Canadian NICUs. Primary outcome was a composite of death or significant NDI (sNDI) at 18-21 months of corrected age. Secondary outcomes included NDI and individual components of the primary outcome. We assessed the relationship between linezolid exposure and outcomes using a multivariable logistic regression. Of 274 infants included, 67 (24.4%) were exposed to linezolid. Median GA was 26 weeks and clinical characteristics were similar between groups. There was no difference in composite outcome of death or sNDI among the infants of both groups, but significantly more death by 18-21 months in the linezolid group (29.9% vs. 17.6%; P = 0.01). Linezolid exposure was not associated with composite outcome of death or sNDI at 18-21 months. The association between linezolid and death may be due to indication bias. Further studies are warranted.

Neurodevelopmental outcome at 2\xa0years of age in preterm infants with late-onset sepsis

Late-onset sepsis is associated with impaired neurodevelopmental outcome in preterm infants. This prospective cohort study aims to establish the effect of sepsis after 72 h of life on cognitive, psychomotor, and language development of preterm infants (below 32 weeks gestational age and/or below 1500 g). At 2 years corrected age, neurodevelopmental outcome was tested using Bayley’s Scales of Infant Development-II, Lexilijst (lexical development questionnaire), and behavior checklists. Of 117 patients included, 85 experienced blood culture–proven infection. Coagulase-negative staphylococci were responsible for 55% of the episodes. No significant differences were found in cognitive, motor, and behavioral scores or lexiquotient comparing patients with versus no proven infection. When comparing three groups (coagulase-negative staphylococci, other, and negative blood culture), a significant difference was found in composite cognitive scores (p = 0.016), in favor of the coagulase-negative staphylococci group versus other causal agent group (p = 0.007). No significant differences were found in other subscales.Conclusion: In this cohort, no differences were found in neurodevelopmental outcome at 2 years corrected age between proven and no proven infection groups; confirmation in larger cohorts with a control group is needed. Patients encountering coagulase-negative staphylococci sepsis showed a significant better cognitive outcome compared to other causal agents.What is Known:• Late-onset sepsis is associated with impaired neurodevelopmental outcome in preterm infants.What is New:• Preterm infants encountering late-onset sepsis by coagulase-negative staphylococci show a better cognitive outcome in comparison to other causal infectious agents in this cohort.• No differences were found in neurodevelopment at 2 years of age in preterm infants with suspected lateonset sepsis, between proven and no proven infection groups. Confirmation is needed in larger cohorts with a substantial control group.

Higher intake of coagulase-negative staphylococci from maternal milk promotes gut colonization with mecA-negative Staphylococcus epidermidis in preterm neonates.

We aimed to determine factors associated with gut colonization of preterm neonates with coagulase-negative staphylococci (CoNS) from maternal milk (MM). CoNS isolated from weekly collected stool and MM of hospitalized preterm (n = 49) and healthy term neonates (n = 20) were genotyped. Colonization-related factors were determined by Cox proportional hazards regression. Gut colonization with mecA-negative Staphylococcus epidermidis from MM was less prevalent (40.8% vs. 95%) and delayed (median age 15.5 vs. 2 days) in preterm compared with term neonates. Enhanced colonization was associated with higher intake of CoNS from MM (hazard ratio (95% confidence interval) 1.006 (1.00-1.01) for 106 colony-forming units), lower proportion of mecA-positive predominant NICU strains in gut (0.09 (0.01-0.49) for 1%) and lower incidence of late-onset CoNS sepsis (5% vs. 34% in those without colonization). Enteral feeding with larger proportion of unpasteurized MM and limiting spread of predominant strains may promote colonization with CoNS from MM.

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.

Cerebral ultrasound abnormalities in preterm infants caused by late-onset sepsis.

IntroductionThis study describes cerebral ultrasound abnormalities caused by late-onset sepsis (LOS) in very preterm infants with a gestational age of < 32 weeks and/or birthweight < 1500 grams.MethodsThe prospective study (“INFANT study”) included 117 preterm infants with suspected LOS. Proven LOS was defined as a positive blood culture after 72 hours of life. In case of coagulase-negative staphylococci an elevated C-reactive protein was additionally required to establish proven LOS. Patients were identified as proven LOS and patients with only clinical symptoms of LOS. Cerebral ultrasound images were obtained in the first week after birth, during/after LOS and before discharge. Cerebral findings were divided in no/minor and major abnormalities.ResultsEighty-six preterm infants had proven LOS and 31 preterm infants had only clinical signs of LOS. Four infants were excluded because pre-existing major brain abnormalities. No significant differences (p = 0.624) for incidence of major brain abnormalities on cerebral ultrasound were found.ConclusionNo differences were revealed in prevalence of major brain abnormalities between the groups with proven LOS and with clinical signs of LOS. Both infants with a gram negative sepsis developed major brain abnormalities, whereas only two of 66 preterm infants coagulase-negative staphylococci sepsis developed major brain abnormalities.

Coagulase negative staphylococcal sepsis in neonates: do we need to adapt vancomycin dose or target?

BackgroundDespite differences in types of infection and causative organisms, pharmacokinetic-pharmacodynamic (PKPD) targets of vancomycin therapy derived from adult studies are suggested for neonates. We aimed to identify doses needed for the attainment of AUC/MIC > 400 and AUC/MIC > 300 in neonates with sepsis and correlate these targets with recommended doses and treatment outcome.MethodsNeonates who had Vancomycin therapeutic drug monitoring (TDM) performed between January 1, 2010 and December 31, 2012 were studied. Clinical characteristics, episodes of Gram-positive sepsis with outcomes and all neonatal blood culture isolates in hospital were collected from medical records. To estimate probability of target attainment of AUC/MIC >400 and AUC/MIC >300 a 1000-subject Monte Carlo simulation was performed by calculating AUC using Anderson’s (Anderson et al. 2006) and TDM trough concentrations (Ctrough) based population PK models.ResultsFinal dataset included 76 patients; 57 with confirmed Gram-positive sepsis. TDM was taken after the 1st to 44th dose. 84.1% of Ctrough were within the range 5–15 mg/L. Currently recommended doses achieved probability of the targets (PTA) of AUC/MIC >400 and AUC/MIC >300 in less than 25% and 40% of cases, respectively. Doses required for 80% PTA of AUC/MIC > 400 for MIC ≥2 mg/L resulted in Ctrough values ≥14 mg/L. Mean AUC/MIC values were similar in treatment failure and success groups.ConclusionWith currently recommended vancomycin dosing the therapeutic target of AUC/MIC > 400 is achieved only by 25% of neonates. Appropriate PKPD targets and respective dosing regimens need to be defined in prospective clinical studies in this population.

What Is the Cost of Coagulase-Negative Staphylococcal Sepsis in the Neonatal Intensive Care Unit (NICU)?

What Is the Cost of Coagulase-Negative Staphylococcal Sepsis in the Neonatal Intensive Care Unit (NICU)?

Association between birth route and late-onset sepsis in very preterm neonates.

To evaluate the association between birth route and late-onset sepsis (LOS), and coagulase-negative Staphylococcal (CONS)-related LOS in preterm neonates. In this observational study, data from 20,038 infants born between 22 and 32 weeks' gestation and admitted to Canadian neonatal intensive care units between 2010 and 2014 were analyzed retrospectively. The impact of birth route on LOS was assessed using univariate analysis and multiple logistic regression. A total of 8218 neonates were born via vaginal route and 11,820 via cesarean section. Incidence rates of LOS for infants born vaginally and via a cesarean section were 13.1 and 13.2%, respectively, and there was no significant difference in odds of LOS between the groups (adjusted odds ratio (AOR): 0.99; 95% CI 0.87 to 1.12); however, the odds of CONS sepsis were higher in the cesarean group (AOR: 1.15; 95% CI: 1.01 to 1.32). Birth route did not have an impact on LOS, but was associated with CONS-related LOS.

Pathogen and antimicrobial resistance profiles of culture-proven neonatal sepsis in Southwest China, 1990-2014.

Neonatal sepsis (NS) sustains high mortality and morbidity in China, but data on the epidemiology and antimicrobial resistance patterns of NS pathogens are limited. The clinical features, aetiology and antimicrobial resistance of culture-proven NS were analysed over a period of 25 years in the metropolitan city of Chongqing in Southwest China. The occurrence rates of neonatal early-onset sepsis (EOS) were found to gradually decrease while late-onset sepsis (LOS) was kept stable from 1990 to 2014. Although coagulase-negative staphylococcus (CoNS) sepsis accounted for most infections, the occurrence rates of CoNS sepsis gradually decreased, especially in EOS. Escherichia coli and Klebsiella were common Gram-negative bacteria. The occurrence rates of E. coli and Klebsiella remained stable in EOS; however, in LOS, those had increased mildly, especially from 2009 to 2014. Although a high-degree resistance to common first- and second-line antimicrobials was observed for the main causative pathogens of NS, the gentamicin-resistance rate declined gradually from the year 2003. Similarly, the ceftazidime-resistance rate of E. coli dropped gradually from the year 2007. The alarmingly high degree of antibiotic resistance calls for urgent evaluation and development of antibiotic policy and protocols for the treatment of NS. Clinicians should strictly control the antibiotics use, decrease invasive manipulations and shorten hospitalisation to prevent LOS.

Letter to the Editor: Prevalence and Antibiotic Resistance of Neonatal Sepsis Pathogens

Dear Editor, We read with great interest the original article by Behmadi et al. (1) in the most recent issue of your journal. We would like to commend the authors for their endeavor but at the same time feel that few necessary clarifications and comments would benefit the general readers of the journal: 1) The abstract mentions that “the aim of this study was to determine the prevalence and evaluate the antimicrobial susceptibility patterns of bacterial infections at a neonatal unit,” but the main text states that the objective was “to determine the frequency and antibiotic resistance of pathogens at the neonatal intensive-care unit (NICU) and neonatal ward of our hospital.” The study, being “crosssectional” in design, is able to give prevalence but not frequency or incidence (2). Furthermore, the pathogens associated with neonatal sepsis include viruses and parasites, in addition to bacteria (3). 2) The authors mention the total number of culture (blood, urine and cerebrospinal fluid (CSF)) samples and their positivity rates, but not the total number of newborns being assessed (sample size). Therefore, the percentage of newborns who ultimately have culture (blood, urine or CSF)-positive sepsis indicative of prevalence of bacterial infection, which is one of the study’s primary objectives, can never be ascertained. 3) The authors do not provide a definition for terms such as “late-onset sepsis” and “clinical findings suggesting urinary tract infection (UTI).” Different epidemiological studies have used cut-offs ranging from 3 to 7 days to define late-onset sepsis, depending on the gestational age and birth weight of the newborn (4). Also, there are no clinical findings that specifically suggest UTI in a newborn. 4) The methodology does not state how the urine sample for bacterial culture was collected. It should ideally be collected by suprapubic aspiration (5); other methods are associated with high chances of contamination. 5) The authors also do not mention whether hospitalacquired infections were included in the late-onset sepsis group. The causative organisms and the antibiotic sensitivity pattern are expected to vary considerably depending on whether the source of infection is the community or a heath care facility (5). Hospital-acquired pathogens could also explain the high prevalence of antibiotic resistance in the isolated organisms. 6) The finding that coagulase-negative staphylococcus (CONS) was the commonest organism in both earlyand late-onset sepsis should be viewed with caution in light of the great controversy about the criteria for defining CONS sepsis in newborns (6). These criteria have often resulted in CONS being overrepresented as a true pathogen in neonatal sepsis (7). In an attempt to decrease falsepositivity rates, various investigators have proposed different diagnostic algorithms based upon quantitative culture and colony count, presence of an indwelling central venous catheter (8) or time to positivity of blood culture (9).

Study of Bacteriological pathogen causing neonatal sepsis at NICU in Ad-din medical college hospital

Objective : To determine the common causative bacterial agents of neonatal sepsis and their antimicrobial susceptibility in NICUMethods : Newborns with clinical signs of septicemia and positive blood culture during twelve months were prospectively studied. Samples for blood cultures, complete blood count, C-reactive protein, sugar, electrolytes were obtained ; ampicillin and gentamycin were started empirically.Result : Seven hundred and three neonates were investigated to rule out of sepsis. The male, female ratio was 1.3:1 and 56(63.63%) of patients were preterm and 32(36.36%) were term neonates. There were 68 (77.27%) cases of Early onset neonatal sepsis (EONS) and 20(22.64%) of Late onset neonatal sepsis (LONS). Coagulase negative staphylococcus (CONS) was the most common 37(42.04%) Gm+ve pathogen causing early onset neonatal sepsis and Acinetobacter was common Gm-ve pathogen in both early onset 16(18%) and late-onset 8 (9%) sepsis. CONS sepsis showed high degree of resistance to commonly used antibiotics; ampicillin (86.5%), oxacillin (60%),cefotaxime (67%) but comparatively low resistance to vancomycin (0%), gentamicin (25%), Levofloxacin(36%) &amp; Imipenem (49%). Acinetobacter were highly resistant to ampicillin (100), gentamicin(75%), cefotaxime(100) and sensitive to Amikacin (58.33%), ciprofloxacin (54.16%), Levofloxacin and Imipenem (62.5%)and Colistin (95.83%).Conclusion : Neonatal sepsis in our NICU is mainly caused by grampositive organisms, which are developing resistance to commonly used antibiotics. The initial empirical choice of Ampicillin and Gentamicin appears to be unreasonable for our environment.Northern International Medical College Journal Vol.5(1) 2013: 297-300

Markedly raised levels of C-reactive protein are associated with culture-proven sepsis or necrotising enterocolitis in extremely preterm neonates.

A serious inflammatory process is suspected when C-reactive protein (CRP) is very high, and we established the causes and outcomes when CRP was >100 mg/L in neonates. We retrospectively reviewed all 277 episodes where CRP exceeded 100 mg/L between January 2007 and December 2011 at a tertiary neonatal unit. Of the 6025 neonates admitted during the study period, 258 had CRP >100 mg/L at least once. The overall mortality rate was 44/258 (17%); 36 died within 7 days of CRP >100 mg/L, and 34 were extremely preterm infants. CRP exceeded 100 mg/L in 106 infants within the first 3 days of life - 74 term, 25 preterm and seven extremely preterm - with no infection identified in 81%. In contrast, infections were found in 87% of the 171 episodes from day four of life - 129 extremely preterm, 23 preterm and 19 term - predominantly coagulase-negative staphylococcus sepsis and necrotising enterocolitis. Markedly elevated CRP in the first 3 days of life was most likely to affect term neonates (74/106) with no infectious cause (81%). However, CRP >100 mg/L from the fourth day of life was most likely to affect extremely preterm neonates (129/171) and have an infectious cause (87%).

Pharmacokinetics of linezolid treatment using intravenous and oral administrations in extremely premature infants.

Vancomycin is the usual antibiotic treatment in coagulase-negative staphylococcus sepsis in premature infants but causes renal toxicity. As linezolid is effective in Gram-positive cocci infection, and devoid of renal side-effects, it has been used in Nantes neonatal intensive care units and linezolid plasma concentrations were monitored. The aims of this study are to report data on linezolid concentrations in premature infants, describe clinical and bacteriological evolution during treatment, and determine potential side effects. A retrospective observational study of premature infants treated with linezolid in Nantes Hospital from January 2008 through November 2011 was conducted. Linezolid plasma concentrations, possible side effects due to linezolid, and clinical response to linezolid treatment were collected from folder review. Twenty-four linezolid plasma concentrations were monitored in 16 premature patients, at steady state for continuous intravenous administration or 7 ± 1.5 h after last oral administration. Except for one case, linezolid plasma concentrations were ≥minimal inhibition concentration (MIC) for linezolid for both parenteral and oral administrations. We observed three cases of thrombocytopenia, two of leukopenia, three of neutropenia, and one of severe hyperlactacidemia, resolving after discontinuation of treatment. Clinical signs of infection resolved in 13/16 cases. Bacteria were coagulase-negative Staphylococci in 12/16 cases and were eradicated in 9/12 evaluable cases. This study reports an adequate linezolid plasma concentration with regard to the linezolid MIC in extremely premature infants. However, considering adverse events reported, its use should be cautious and may concern only oral administration during the late phase of infection, to limit paradoxical catheter use to treat nosocomial infections. Moreover, safe and efficient anti-Staphylococcus therapies should be identified to treat this vulnerable population.

Frequent nasopharyngeal suctioning as a risk factor associated with neonatal coagulase-negative staphylococcal colonisation and sepsis.

This case-control study aimed to determine whether catheter use was significantly associated with coagulase-negative staphylococci (CoNS) colonisation and/or sepsis in neonates. Weekly swabs of the nose, umbilicus, rectum, wounds, eye discharge and intravenous catheter tips (after removal) of infants admitted to the neonatal intensive care unit of Universiti Kebangsaan Malaysia Medical Centre, Malaysia, were cultured. CoNS sepsis was diagnosed if pure growth of CoNS was cultured from the peripheral blood specimen of symptomatic infants. For each infant with CoNS colonisation or sepsis, a control infant was retrospectively and randomly selected from unaffected infants in the ward. Multivariate analyses were performed to determine whether catheter use was a significant risk factor. CoNS colonisation was detected in 113 (8.7%) infants. CoNS sepsis was found in 12 (10.6%) infants with CoNS colonisation and 7 (0.6%) infants without CoNS colonisation. Multivariate analysis showed that the following were significantly associated with CoNS colonisation: conjunctivitis (adjusted odds ratio [OR] 8.2, 95% confidence interval [CI] 1.9–34.8, p = 0.005); central venous catheters (adjusted OR 5.8, 95% CI 1.9–17.8, p = 0.002); and nasopharyngeal and/or oral suctioning more than twice in the 48 hours before positive culture (adjusted OR 7.3, 95% CI 3.3–16.2, p < 0.001). Exposure to frequent nasopharyngeal and/or oral suctioning (adjusted OR 20.8, 95% CI 3.5–125.3, p = 0.001) was the only significant factor associated with CoNS sepsis. Infants requiring more than two nasopharyngeal and/or oral suctions in the previous 48 hours were found to have a higher risk of developing CoNS colonisation and sepsis.

PC.33 Quality Improvement in use of Vancomycin dosing regimens

BackgroundLate onset sepsis (>48 hr of life) in neonates is predominantly caused by coagulase negative staphylococci (CoNS).1 Vancomycin remains the most frequently used antibiotic to treat CoNS sepsis. It is...