Cause Of Late-onset Sepsis Research Articles

Treatment of Methicillin-Resistant Staphylococcus aureus in Neonatal Mice: Lysostaphin Versus Vancomycin

S. aureus is a significant cause of late-onset sepsis in neonates. Increasing antibiotic resistance, however, requires additional treatment options. Lysostaphin, an endopeptidase, has that potential. The objective of this study is to compare lysostaphin versus vancomycin against methicillin-resistant Staphylococcus aureus (MRSA) in a neonatal mouse model. Minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) against MRSA strain USA300 were determined using standard methods. To determine pharmacokinetics, neonatal pups received either vancomycin or lysostaphin intraperitoneal and serum samples were obtained. To evaluate efficacy, pups were infected s.c. and littermates randomized to receive either saline, vancomycin, or lysostaphin intraperitoneal. Pups were observed for survival and growth. Quantitative blood cultures were obtained 24 h after infection. The MIC/MBC for vancomycin and lysostaphin were 0.71/1.19 microg/mL and <0.008/0.015 microg/mL, respectively. Mean lysostaphin concentrations ranged from 2.34 to 8.92 microg/mL. Mean vancomycin concentrations ranged from 1.72 to 11.2 microg/mL. Lysostaphin improved survival compared with placebo (p < 0.00001) and vancomycin (p < 0.03). There was no significant difference in growth among the groups. All treatment regimens resulted in less bacteremia compared with placebo (p < 0.0001). Lysostaphin appears to be more effective than vancomycin in treating MRSA in a neonatal model.

Fungal Prophylaxis in the Neonatal Intensive Care Unit

Candida sp are the third most common cause of late-onset sepsis (occurring at &amp;gt;72 hours of age) in very low-birthweight (VLBW) infants (birthweight ≤1,500 g). Invasive candidiasis may cause death or neurodevelopmental impairment in almost 75% of infected extremely low-birthweight (ELBW) infants (birthweight ≤1,000 g). Preventive strategies are urgently needed to improve on these poor outcomes. The antifungal agent fluconazole is an ideal candidate prophylactic agent. Its pharmacokinetic properties and distribution allow for low doses and extended intervals while maintaining high tissue concentrations. In the past decade, four randomized, controlled trials and seven retrospective cohort studies have evaluated fluconazole prophylaxis for the prevention of fungal infection in ELBW or VLBW infants. These studies have shown that fluconazole treatment significantly reduces Candida infection rates with a concomitant reduction in Candida-related mortality. To date, fluconazole prophylaxis has not been associated with adverse events or with the emergence of fluconazole-resistant Candida sp. Although further studies may provide information to allow targeting of prophylaxis to infants at highest risk, fluconazole prophylaxis should be strongly considered in a time-limited fashion, especially in neonatal intensive care units that have higher-than-baseline rates of Candida infection, in infants weighing less than 1,000 g at birth, and for those who have significant ongoing risk factors.

Candidal versus bacterial late-onset sepsis in very low birthweight infants in Israel: a national survey

Candidal infections are one of the common causes of late-onset sepsis (LOS) among very low birthweight (VLBW) infants, and are associated with substantial morbidity and mortality. The aim of this study was to evaluate the perinatal and neonatal risk factors for fungal LOS compared with bacterial LOS in VLBW infants. This was a population-based observational study of VLBW infants in 28 neonatal intensive care units across Israel, with information on 11,830 infants born between 1995 and 2002 from the Israeli National VLBW infant database. The study population comprised 3054 infants with one or more episodes of LOS. Univariate analysis and logistic regression models were used to compare perinatal and neonatal risk factors between infants with fungal sepsis only (N=179) and those with bacterial sepsis only (N=2630). The mean birthweight and gestational age of infants with candidal LOS were significantly lower (940 g; 27.1 weeks) than those in the bacterial LOS group (1027 g; 28.3 weeks) (P<0.001). Logistic regression analysis showed that candidal sepsis, in contrast to bacterial sepsis, was independently associated with decreasing gestational age and bronchopulmonary dysplasia (BPD). In addition, BPD only [odds ratio (OR) 1.84; 95% confidence intervals (CI) 1.03-3.23] and BPD with postnatal steroid therapy (OR 2.66; 95% CI 1.59-4.46) were independently associated with an increased risk for candidal sepsis.

Persistent Bacteremia and Severe Thrombocytopenia Caused by Coagulase-NegativeStaphylococcusin a Neonatal Intensive Care Unit

Coagulase-negative Staphylococcus (CoNS) is the most frequent cause of late-onset sepsis in NICUs, but mortality is rare and morbidity is unusual. We report a new syndrome of CoNS sepsis characterized by significant morbidity and persistent bacteremia despite aggressive antibiotic therapy and no identified focus of infection. We conducted a retrospective review of infants in the NICU with CoNS bacteremia between 2000 and 2002. Statistical analysis included an initial exploratory analysis followed by logistic regression. Microbiological identification of all isolates and molecular typing were performed. Thirty-one neonates with persistent CoNS bacteremia were compared with 60 randomly selected neonates from a group of 140 with nonpersistent CoNS bacteremia. The clinical manifestations at presentation, gestational ages, and birth weights were similar in the 2 groups. Thrombocytopenia was present in 26 (84%) neonates with persistent CoNS bacteremia but only in 8 (13%) neonates in the nonpersistent group. Central venous catheterization increased the risk for persistent CoNS bacteremia, but 42% of the persistent group was never catheterized. Staphylococcus epidermidis was the most common isolate in both groups. Molecular typing failed to identify a predominant clone. The syndrome of persistent CoNS septicemia is remarkable for thrombocytopenia and persistence in the absence of central venous catheterization. Clinical manifestations at presentation and demographic characteristics did not discriminate between the persistent and nonpersistent groups. We did not identify the emergence of a particularly virulent clone, but it is possible that some strains of CoNS have acquired the capacity to persist under different conditions.

Cloxacillin versus vancomycin for presumed late-onset sepsis in the Neonatal Intensive Care Unit and the impact upon outcome of coagulase negative staphylococcal bacteremia: a retrospective cohort study

BackgroundCoagulase negative staphylococcus (CONS) is the main cause of late-onset sepsis in Neonatal Intensive Care Units (NICU). Although CONS rarely causes fulminant sepsis, vancomycin is frequently used as empiric therapy. Indiscriminate use of vancomycin has been linked to the emergence of vancomycin resistant organisms. The objective of this study was to compare duration of CONS sepsis and mortality before and after implementation of a policy of selective vancomycin use and compare use of vancomycin between the 2 time periods.MethodsA retrospective study was conducted of infants ≥4 days old, experiencing signs of sepsis with a first positive blood culture for CONS, during two 12-month periods. Late-onset sepsis was treated empirically with vancomycin and gentamicin during period 1, and cloxacillin and gentamicin during period 2. The confidence interval method was used to assess non-inferiority of the outcomes between the two study groups.ResultsThere were 45 episodes of CONS sepsis during period 1 and 37 during period 2. Duration of sepsis was similar between periods (hazard ratio of 1.00, 95%CI: 0.64, 1.57). One death during period 2 was possibly related to CONS sepsis versus none in period 1. Vancomycin was used in 97.8% of episodes in period 1 versus 81.1% of episodes in period 2.ConclusionAlthough we failed to show non-inferiority of duration of sepsis in the cloxacillin and gentamicin group compared to the vancomycin and gentamicin group, duration of sepsis was clinically similar. Restricting vancomycin for confirmed cases of CONS sepsis resistant to oxacillin appears effective and safe, and significantly reduces vancomycin use in the NICU.

173 Fungal Colonization of Newborn in Neonatal Intensive Care Unit: A Prospective Study

Background. Invasive candidiasis in neonates has become an increasing problem over the past decade in Neonatal Intensive Care Units (NICUs) in the world; it is a relatively common cause of late onset sepsis associated with a high mortality. Risk factors are preterm babies who require invasive diagnostic and aggressive therapeutic procedures, prior antibiotic therapy, congenital abnormalities, gastrointestinal tract diseases, necrotizing enterocolitis and anatomical abnormalities requiring surgery. Prior colonization is the major risk factor for candidemia. Methods. To determine the rate of colonization, risk factors and the possible modes of acquisition of Candida spp. In neonates in NICU, we conducted a prospective cohort study including 48 successive admissions at NICU of Pediatric University Hospital, Sarajevo, during 3 months. Samples (mucocutaneous swabs, urine, stool, blood) were obtained weekly until the time of discharge or death (one infant enrolled in the study exited). Care health worker hands were cultured weekly (55 samples). Results. Candida spp. from various body sites samples were isolated in 7 patients (rate of colonization 14,8%) while 7 samples of health workers hands were positive for C. spp (14,5%). Patients colonizated or infected by Candida spp. In our study were or very preterm newborns (3/7) or compromised term newborns (4/7), with congenital abnormalities (2/7) or gastrointestinal surgical interventions (2/7). Two very preterm neonates were colonized early from the birth, which indicates possible vertical transmission. In other 5 patients, colonization occurred more lately, after at least 15 days stay in NICU, which indicates nosocomial transmission as a predominant mode of acquisition. Among 10 positive patterns from different body sites, Candida albicans was isolated in 6 cases; other 4 cases were C. glabrata (2/10), C. krusei (1/10) and C. famata (1/10). Conclusions. Rather than focusing on methods of identifying of pregnant women with vaginal Candida colonization, attention should be directed to high risk neonates and infection control measures including hands washing by health care workers.

Antifungal Agents and Fungal Prophylaxis in the Neonate

After completing this article, readers should be able to: 1. Delineate the third most common cause of late-onset sepsis in very low-birthweight infants. 2. Describe the primary predictors for successful treatment of potential fungal sepsis and culture-positive sepsis. 3. List the gold standard for antifungal therapy in the neonate. 4. Compare and contrast liposomal amphotericin B and amphotericin B and describe the neonates in whom liposomal amphotericin B should be used. 5. Describe the situation in which antifungal prophylaxis may be appropriate. Among the 6,956 very low-birthweight (VLBW) (<1,500 g) infants reported to the National Institute of Child Health and Human Development between 1998 and 2000, Candida albicans was the third most frequent organism isolated (76/1313, 6%), following coagulase-negative Staphylococcus and S aureus , in episodes of late-onset sepsis. (1) Candida sp were responsible for 12.2% of first episodes of late-onset disease. (1) Because of a mortality rate as high as 25% (32% in the recent study by Stoll and associates (1)) for septicemia and 36% for meningitis as well as an 11-fold increase in the incidence of such infection over the previous 15 years, early initiation of therapy is imperative. (2)(3) Unfortunately, the mean delay between initial positive blood culture and commencement of antifungal treatment varies from 2.1±1.3 days to 5.1±3 days, and a significant number of infants are not diagnosed until autopsy. (4) Delayed treatment may reflect not only an increased risk of mortality, but also increased rates of intraventricular hemorrhage, chronic lung disease, retinopathy of prematurity requiring surgical therapy, and up to a fourfold increase in long-term neurodevelopmental delays. Early recognition and therapy as well as the removal of central lines remain the most important predictors of successful treatment. (5) In a recent study by Rowen and colleagues (6) in which questionnaires were distributed to United States-based members of …

Phenotypic and genotypic characterisation of blood isolates of coagulase-negative staphylococci in the newborn.

Coagulase-negative staphylococci (CNS) are the leading cause of late-onset sepsis in newborns (>72 h of age). Our aim was to determine whether phenotypic and/or genotypic differences existed between blood isolates of CNS regarded as inducers of sepsis or as contaminants. Ninety-seven bloodisolates of CNS recovered from newborns at the neonatal intensive care unit, Orebro, Sweden in 1983-1997 were analysed. Twenty-nine of them (30%) were classified as sepsis isolates and 68 (70%) as contaminants. The most prevalent species was Staphylococcus epidermidis (n=59). Staphylococcus haemolyticus (n=16) was most often isolated from newborns with the lowest gestational age and birth weight. Biochemical typing using the Phene Plate system (PhP) and genotyping using pulsed-field gel electrophoresis (PFGE) showed that the S. epidermidis isolates regarded as inducers of sepsis (n=16) were more homogeneous than isolates considered contaminants (n=37). One main genotypic group, representing seven (44%) isolates, was identified among the sepsis isolates. Phenotypically the S. epidermidis sepsis isolates comprised three major clusters. In contrast, among the S. epidermidis contaminants, eight genotypic groups and two phenotypic clusters were identified. The dominating genotypic group among the sepsis isolates of S. epidermidis may represent strains with higher invasive capacity.

Risk factors for candidemia in Neonatal Intensive Care Unit patients. The National Epidemiology of Mycosis Survey study group.

Candida species are important nosocomial pathogens in neonatal intensive care unit (NICU) patients. A prospective cohort study was performed in six geographically diverse NICUs from 1993 to 1995 to determine the incidence of and risk factors for candidemia, including the role of gastrointestinal (GI) tract colonization. Study procedures included rectal swabs to detect fungal colonization and active surveillance to identify risk factors for candidemia. Candida strains obtained from the GI tract and blood were analyzed by pulsed field gel electrophoresis to determine whether colonizing strains caused candidemia. In all, 2,847 infants were enrolled and 35 (1.2%) developed candidemia (12.3 cases per 1,000 patient discharges or 0.63 case per 1,000 catheter days) including 23 of 421 (5.5%) babies < or =1,000 g. After adjusting for birth weight and abdominal surgery, forward multivariate logistic regression analysis demonstrated significant risk factors, including gestational age <32 weeks, 5-min Apgar <5; shock, disseminated intravascular coagulopathy, prior use of intralipid, parenteral nutrition, central venous catheters, H2 blockers, intubation or length of stay > 7 days before candidemia (P < 0.05). Catheters, steroids and GI tract colonization were not independent risk factors, but GI tract colonization preceded candidemia in 15 of 35 (43%) case patients. Candida spp. are an important cause of late onset sepsis in NICU patients. The incidence of candidemia might be decreased by the judicious use of treatments identified as risk factors and avoiding H2 blockers.

Late-onset infections of infants in neonatal units.

To examine regional variations in the incidence of late-onset neonatal infections in Australian and New Zealand neonatal units. A longitudinal, prospective surveillance study of systemic sepsis (septicaemia or meningitis) in 11 neonatal units: 10 in the Australian States of the Northern Territory, New South Wales, Queensland, Victoria and Western Australia, and 1 in Christchurch, New Zealand. The results are reported of late-onset neonatal infection (defined as sepsis after 48 h) for the second year of prospective surveillance, data being collected from 1 October 1992 to 30 September 1993. Data were available on 24535 live births in Australia, representing approximately 10% of all live births in the country. There were 320 episodes of sepsis in Australian units affecting 294 babies. One hundred of these episodes (31%) were early-onset; 3.0% of babies admitted to six tertiary care neonatal units attached to maternity hospitals developed late sepsis, and this rate did not differ between units. The proportion of babies infected was inversely related to birthweight: 22.6% of babies under 1OOOg, but 0.6% over 2000g. Coagulase negative staphylococci were the commonest cause of late-onset sepsis. There were 26 episodes of S. aureus septicaemia, of which only one was due to MRSA. Meningitis occurred in 13 babies (5.9%) with late-onset sepsis. The mortality from late-onset sepsis was 7.7%. Coagulase-negative staphylococci are the commonest cause of late-onset sepsis of babies in neonatal units. There were no major regional differences in the incidence of, or the organisms causing, late sepsis.

Surveillance of colonization and late-onset septicaemia in neonates

Twenty-seven newborns had an episode of late-onset sepsis (septicaemia or bacterial meningitis after 48 h of age) over an 18 month period. Preceding or simultaneous surface cultures were available from 26 babies. Colonization with the organism causing sepsis could only be documented in 10 cases. Colonization with aminoglycoside-resistant Gram negative organisms was common but there were only two cases of systemic sepsis with a resistant organism. Pseudomonas aeruginosa frequently colonized babies over the first 8 months of the survey, but subsequently virtually ceased to colonize babies, although it continued to be a common cause of late-onset sepsis. These findings do not support the utility of routine surveillance of organisms colonizing neonates in predicting bacteria causing late-onset sepsis. They also cast doubt on the value of eliminating colonizing organisms by expensive infection control measures.