Bacterial Infection In Newborns Research Articles

Anti bacterial function of secreted human FABP3

FABP3 belongs to a large family of cytoplasmic fatty acid binding proteins that are expressed in a tissue-specific manner. It is predominantly expressed in breast, muscle and heart. During our exploratory studies on the role of FABP3 in tumorigenesis and our consequent attempts to study the molecular mechanism responsible for the oncogenic potential of FABP3, we came across an unexpected role of FABP3 as an anti-bacterial protein. Presence of the protein was detected in culture media of cell lines stably over-expressing human FABP3. Conditioned medium from these FABP3 over-expressing cells exerted a distinct anti-bacterial activity against E. coli. Our results indicate that binding of FABP3 to the bacterial cell surface contributes to its anti-bacterial activity. Incubation of E. coli bacterial cells with FABP3 protein led to disruption of the physical integrity of bacterial cell membrane causing leakage of cellular components. Further, in silico analysis predicted strong binding of FABP3 to the antibiotic binding sites on the bacterial ribosome. Interestingly, we found that FABP3 is a naturally occurring secretory protein present in milk in abundance as confirmed by western blot and ELISA. Thus, our experimental data together with in silico analysis suggests that FABP3 is secreted in milk, has an anti-bacterial function, shows activity against E. coli by disrupting bacterial membrane and targeting the ribosome, and may play a protective role against bacterial infection in newborns.

Early-onset group B streptococcal disease in African countries and maternal vaccination strategies.

Invasive group B streptococcal (GBS) disease is the commonest perinatally-acquired bacterial infection in newborns; the burden is higher in African countries where intrapartum antibiotic prophylaxis strategies are not feasible. In sub-Saharan Africa, almost one in four newborns with GBS early-onset disease will demise, and one in ten survivors have moderate or severe neurodevelopmental impairment. A maternal GBS vaccine to prevent invasive GBS disease in infancy is a pragmatic and cost-effective preventative strategy for Africa. Hexavalent polysaccharide protein conjugate and Alpha family surface protein vaccines are undergoing phase II clinical trials. Vaccine licensure may be facilitated by demonstrating safety and immunological correlates/thresholds suggestive of protection against invasive GBS disease. This will then be followed by phase IV effectiveness studies to assess the burden of GBS vaccine preventable disease, including the effect on all-cause neonatal infections, neonatal deaths and stillbirths.

Structural Identification of Lipid-α: A Glycosyl Lipid Involved in Oligo- And Polysaccharides Metabolism in Streptococcus agalactiae (Group B Streptococcus).

Streptococcus agalactiae (group B Streptococcus, GBS) is a gram-positive bacterium that is an asymptomatic colonizer commonly found in the gastrointestinal and genitourinary tract of healthy adults. GBS is also the most common cause of life-threatening bacterial infections in newborns and is emerging as a pathogen in immunocompromised and diabetic adults. The GBS cell wall and covalently linked capsular polysaccharides (CPS) are vital to the protection of the bacterial cell and act as virulence factors. GBS-CPS have been successfully used to produce conjugate vaccines for all currently identified GBS serotypes. However, the mechanisms of biosynthesis and assembly of CPS and the other cell wall components remain poorly defined due to their complex surface structures. In this biosynthetic study of the GBS cell wall-CPS complex, glycolipids with varying lengths of glycosyl-chains were discovered. Among those, one of the smallest glycolipids (named GBS Lipid-α) was structurally characterized. Lipid-α is involved in GBS saccharide metabolism and presumably acts as a glycosyl acceptor to elongate the glycosyl chain. GBS Lipid-α was determined to be a 3-monosaccharide 1,2 acyl glycerol with a molecular mass in the range of m/z = 724-808. GBS Lipid-α is highly heterogenic with various acyl groups and glycosyl moieties. This knowledge will pave the way for future studies to elucidate the entire metabolic pathway and genes involved. The Lipid-α pathway may also exist in other bacterial species and has the potential to be a biomarker for future drug development.

Clinical features of the course and new approaches to the treatment of intrauterine viral and bacterial infections in newborns

Aim. To study the clinical features of the course and new approaches to the treatment of intrauterine viral and bacterial infections in newborns.Materials and methods. Clinical features of the course and new approaches to the treatment of intrauterine viral and bacterial infections in 98 newborns were studied based on the state institution of the National Medical Center of the Republic of Tajikistan “Shifobakhsh” in the Department of neonatal pathology.Results and discussion. We examined 98 patients with intrauterine viral and bacterial infections, which made up the main group, and 20 patients of the control group of the study. The diagnosis of intrauterine viral-bacterial infections of newborns was verified based on serological and immunological, clinical, biochemical, and bacteriological studies of blood and loci.Conclusion. The use of specific therapy in combination with metabolic agents and immunocoregulatory therapy in patients with intrauterine viral and bacterial infections leads to a faster positive dynamic of the main clinical manifestations of the disease.

Late Neonatal Bacterial Infection at the Brazzaville Teaching Hospital

Background: Late Neonatal Bacterial Infection (LNNBI) is a clinical and biological manifestations related to penetration and growth of specific causative bacteria in bloodstream occurring on the 4th-28th day of life. LNNBI still represents an important cause of mortality and morbidity among infants. Objectives: To determine the frequency of late bacterial infections in newborns, to describe the clinical and biological profiles and to identify the main responsible germs. Methods: Descriptive study data collection, conducted over a period of 10 months at the Brazzaville Teaching Hospital, of interest to newborns admitted from the 4th day of life for suspicion of neonatal infection, and those admitted for any other pathology and having presented an infection 48 hours after hospitalization, and in whom a bacterial culture and/or an inflammatory assessment confirmed or suspected infection. Results: During the study period, 1682 newborns were hospitalized, and 86 were hospitalized for a late neonatal bacterial infection, i.e. a frequency of 5.1%. There were 67 (77.9%) community infections and 19 (22.1%) nosocomial infections. The frequency of nosocomial infection was 1.1%. The main signs were fever in 65 cases (75.6%), and respiratory distress in 37 cases (43%). The most frequent localizations were bacteremia 32 (37.2%), pulmonary 21 (24.4%), digestive and meningeal in 11 cases (12.8%) each. The most common germ Klebsiella in 10 (50%) newborns was resistant to the usual antibiotics. The evolution was favorable in 71 cases (82.5%), and death occurred in 12 cases (14%). Conclusion: Late neonatal bacterial infection is common. The main responsible germs are gram-negative bacilli, in particular Klebsiella multi-resistant.

Molecular imprinting based electrochemical biosensor for identification of serum amyloid A (SAA), a neonatal sepsis biomarker

Neonatal septicemia is a bacterial infection in newborns. It is caused by bacteria including Escherichia coli and Group B Streptococcus (GBS). Neonatal septicemia is divided into early-onset and late-onset sepsis. The diagnosis of neonatal septicemia is a challenging task because of the presence of nonspecific symptoms. Biomarkers such as C-reactive protein (CRP), procalcitonin (PCT), and serum amyloid A (SAA) can help in the detection of sepsis at early stages. The level of biomarkers is elevated once sepsis occurs in the body. This study presents the development of an electrochemical biosensor based on nanomaterials integrated molecularly imprinted polymer technique. To obtain the synergistic effect and high conductivity, multi-walled carbon nanotubes (MWCNTs), manganese oxide nanospheres (MnO2NSs), and cobalt oxide nanoparticles (Co3O4NPs) were coated over the screen-printed electrode (SPE). A further modification was done by polymerizing molecularly imprinted polymer (MIP) specifically synthesized for SAA onto modified SPE. The performance of the designed platform was evaluated through electrochemical techniques. The operating range of the developed sensor was found to be 0.01 pM to 1 μM and 0.01 pM as the lower detection limit.

Simplified Dosing Regimens for Gentamicin in Neonatal Sepsis.

Background: The effectiveness of antibiotics for the treatment of severe bacterial infections in newborns in resource-limited settings has been determined by empirical evidence. However, such an approach does not warrant optimal exposure to antibiotic agents, which are known to show different disposition characteristics in this population. Here we evaluate the rationale for a simplified regimen of gentamicin taking into account the effect of body size and organ maturation on pharmacokinetics. The analysis is supported by efficacy data from a series of clinical trials in this population. Methods: A previously published pharmacokinetic model was used to simulate gentamicin concentration vs. time profiles in a virtual cohort of neonates. Model predictive performance was assessed by supplementary external validation procedures using therapeutic drug monitoring data collected in neonates and young infants with or without sepsis. Subsequently, clinical trial simulations were performed to characterize the exposure to intra-muscular gentamicin after a q.d. regimen. The selection of a simplified regimen was based on peak and trough drug levels during the course of treatment. Results: In contrast to current World Health Organization guidelines, which recommend gentamicin doses between 5 and 7.5 mg/kg, our analysis shows that gentamicin can be used as a fixed dose regimen according to three weight-bands: 10 mg for patients with body weight <2.5 kg, 16 mg for patients with body weight between 2.5 and 4 kg, and 30 mg for those with body weight >4 kg. Conclusion: The choice of the dose of an antibiotic must be supported by a strong scientific rationale, taking into account the differences in drug disposition in the target patient population. Our analysis reveals that a simplified regimen is feasible and could be used in resource-limited settings for the treatment of sepsis in neonates and young infants with sepsis aged 0–59 days.

Evaluation of Associated Markers of Neonatal Pathological Jaundice Due to Bacterial Infection.

Background:To evaluate changes of associated markers in neonatal pathological jaundice due to bacterial infection in newborns, to provide an experimental basis for early diagnosis and treatment of neonatal pathological jaundice.Methods:A total of 126 newborns with neonatal pathological jaundice in the Pediatrics Department of Qilu Hospital (Qingdao), Cheeloo College of Medicine, Shandong University from Jan 2016 to Jun 2018 were enrolled. The patients were divided into bacterial infection group (76 cases with combined bacterial infection) and non-infection group (50 cases without bacterial infection). Peripheral blood was drawn from patients, and levels of inflammatory factors, levels of indexes of liver function and levels of cardiac markers were detected. Correlation between inflammatory factors and neonatal pathological jaundice was assessed.Results:The levels of WBC, hs-CRP and PCT in the bacterial infection group were significantly higher than those in the non-infected group (P<0.05). The level of TRF in the bacterial infection group was significantly lower than that in the non-infection group (P<0.01). In the bacterial infection group, the levels of WBC, hs-CRP, PCT, and TRF were positively correlated with the levels of CK, CKMB, LDH, and α-HBDB, respectively (all P<0.05). The TRF level after treatment was significantly higher than that before treatment (P<0.01).Conclusion:Markers such as WBC, hs-CRP, PCT, and TRF can be used as effective indicators in diagnosis of pathological jaundice due to bacterial infection in newborns. The combined testing of WBC, hs-CRP, PCT, and TRF was helpful for early diagnosis and early clinical intervention of neonatal pathological jaundice, which can lower the risk of clinical complications.

Characterization of Clinical and Carrier Streptococcus agalactiae and Prophage Contribution to the Strain Variability.

Streptococcus agalactiae (group B Streptococcus, GBS) represents a leading cause of invasive bacterial infections in newborns and is also responsible for diseases in older and immunocompromised adults. Prophages represent an important factor contributing to the genome plasticity and evolution of new strains. In the present study, prophage content was analyzed in human GBS isolates. Thirty-seven prophages were identified in genomes of 20 representative sequenced strains. On the basis of the sequence comparison, we divided the prophages into eight groups named A–H. This division also corresponded to the clustering of phage integrase, even though several different integration sites were observed in some relative prophages. Next, PCR method was used for detection of the prophages in 123 GBS strains from adult hospitalized patients and from pregnancy screening. At least one prophage was present in 105 isolates (85%). The highest prevalence was observed for prophage group A (71%) and satellite prophage group B (62%). Other groups were detected infrequently (1–6%). Prophage distribution did not differ between clinical and screening strains, but it was unevenly distributed in MLST (multi locus sequence typing) sequence types. High content of full-length and satellite prophages detected in present study implies that prophages could be beneficial for the host bacterium and could contribute to evolution of more adapted strains.

Skin and subcutaneous cell tissue bacterial infections in newborns

Bacterial skin infections are especially common in children of tropical regions, varying clinically from a process superficial (such as folliculitis), to a deeper infection (such as necrotizing fasciitis). Infections of skin and subcutaneous tissue are frequent reasons for medical consultations in primary health care services and hospitalization in pediatric patients. In neonates several factors confer an increased susceptibility to bacterial infections of the skin and its complications. Herein, we review essential aspects of the main bacterial skin infections in newborns and nurselings.

Human milk oligosaccharides inhibit growth of group B Streptococcus

Streptococcus agalactiae (group B Streptococcus, GBS) is a leading cause of invasive bacterial infections in newborns, typically acquired vertically during childbirth secondary to maternal vaginal colonization. Human milk oligosaccharides (HMOs) have important nutritional and biological activities that guide the development of the immune system of the infant and shape the composition of normal gut microbiota. In this manner, HMOs help protect against pathogen colonization and reduce the risk of infection. In the course of our studies of HMO-microbial interactions, we unexpectedly uncovered a novel HMO property to directly inhibit the growth of GBS independent of host immunity. By separating different HMO fractions through multidimensional chromatography, we found the bacteriostatic activity to be confined to specific non-sialylated HMOs and synergistic with a number of conventional antibiotic agents. Phenotypic screening of a GBS transposon insertion library identified a mutation within a GBS-specific gene encoding a putative glycosyltransferase that confers resistance to HMOs, suggesting that HMOs may function as an alternative substrate to modify a GBS component in a manner that impairs growth kinetics. Our study uncovers a unique antibacterial role for HMOs against a leading neonatal pathogen and expands the potential therapeutic utility of these versatile molecules.

Incidence and Risk Factors for Neonatal Jaundice among Neonates with Urinary Tract Infection in Abha, Saudi Arabia

Background: Hyperbilirubinemia is one of the presenting signs of bacterial infection in newborns, and the association of neonatal jaundice with urinary tract infection (UTI) has been particularly emphasized. The aim of this study was to determine the prevalence of UTI in asymptomatic jaundiced neonates younger than 4 weeks old. Method: A cross sectional survey has been conducted at Newborn Unit of Maternity & Pediatrics Hospital – Abha from January 2016 to August 2016. A total of 15 patients have been included in the study, who were diagnosed with hyperbilirubinemia due to urinary tract infection (UTI) after exclusion of unrelated criteria. Conclusion: It could be concluded that UTI should be routinely investigated in early (⩽10 days) idiopathic neonatal jaundice in which all other etiologic factors of neonatal hyperbilirubinemia are ruled out, and the presence of UTI should be considered in case of a poor phototherapy response in cases receiving phototherapy.

The application of heparin-binding protein in the diagnosis of early onset neonatal bacterial infection in newborns

The application of heparin-binding protein in the diagnosis of early onset neonatal bacterial infection in newborns

Significance of combined detection of procalcitonin, C-reactive protein and lipopolysaccharide for early diagnosis of bacterial infection in newborns

Objective To study the significance of combined detection of procalcitonin(PCT), C-reactive protein(CRP) and lipopolysaccharide(LPS) for early diagnosis of bacterial infection in newborns. Methods Clinical data of ninety-eight newborns from neonatal ward of our hospital were retrospectively studied.Fifty cases with bacterial infectious diseases were selected as infection group, in the same period, 48 cases with non-bacterial infectious diseases were selected as control group.In the 24 hours after admission before use of antibiotics, all of cases were picked blood used for testing CRP, PCT, LPS and blood culture, and the results were contrasted and analyzed. Results The levels of serum PCT, CRP and LPS in infection group were respectively significantly higher than those in control group, and the differences were statistically significant(P<0.05, respectively). In gram-positive bacterium group, the positive rate of combined detection of serum PCT and CRP was obviously higher than that of single detection of PCT or CRP(91.3% vs.60.9%, P<0.05; 91.3% vs.56.5%, P<0.05 respectively). In gram-negative bacteria group, positive rate of combined detection of serum PCT and LPS was obviously higher than that of single detection of PCT or LPS respectively(88.9% vs.59.3%, P<0.05; 88.9% vs.66.7%, P<0.05 respectively). Conclusion Joint detection can improve the diagnostic efficiency, and reduce missed diagnosis.And we can identify disease which predominantly infected by positive bacteria or negative bacteria through joint detection, which can contribute to the choice of clinical antibiotic drugs. Key words: Bacterial infection; C-reactive protein; Procalcitonin; Lipopolysaccharide

Human Milk Oligosaccharides Protect Against Enteropathogenic Escherichia coli Attachment In Vitro and EPEC Colonization in Suckling Mice

Breast-feeding reduces the risk of enteric bacterial infections in newborns in part because of human milk oligosaccharides (HMOs), complex glycans that are present in human milk, but not in infant formula. Enteropathogenic Escherichia coli (EPEC) are attaching/effacing pathogens that cause serious diarrheal illness with potentially high mortality in infants. We isolated HMOs from pooled human milk and found that they significantly reduce EPEC attachment to cultured epithelial cells. In suckling mice, administration of HMOs significantly reduced colonization with EPEC compared with untreated controls. These data suggest an essential role for HMOs in the prevention of EPEC infections in human infants.

Community-based Treatment of Serious Bacterial Infections in Newborns and Young Infants

Sepsis in the neonatal period is a major cause of child mortality in low-income countries. Hospitalization and parenteral penicillin/ampicillin and gentamicin therapy are recommended for management. Many families, however, are unable to access hospital care, and most home-delivered newborns who develop sepsis die without receiving antibiotic therapy. Appropriate community-based therapy in such situations is undefined. We compared failure rates of 3 clinic-based antibiotic regimens in 0- to 59-day-old infants with possible serious bacterial infection whose families refused hospitalization in Karachi communities with high neonatal mortality rates>45/1000 live births. Eligible infants were randomly assigned to 7 days of: (1) procaine penicillin [50,000 units/kg once daily (OD) by intramuscular injection (IM)] and gentamicin (5 mg/kg OD IM) reference arm, (2) ceftriaxone (50 mg/kg OD IM), or (3) oral trimethoprim-sulfamethoxazole (TMP-SMX) at 10 mg/kg/day divided twice daily and gentamicin IM OD. Primary outcome was treatment failure, defined as death, deterioration in clinical condition during therapy or no improvement after 2 days. Possible serious bacterial infection was diagnosed in 704 infants, among 5766 screened. Among 434 (61.6%) randomized to clinic-based therapy, there were 13 of 145 failures with penicillin-gentamicin, 22 of 145 with ceftriaxone and 26 of 143 with TMP-SMX-gentamicin. Treatment failure was significantly higher with TMP-SMX-gentamicin compared with penicillin-gentamicin [relative risk 2.03, 95% confidence interval: 1.09-3.79] by intention-to-treat analysis. Differences were not significant in the ceftriaxone versus penicillin-gentamicin comparison [relative risk 1.69, 95% confidence interval 0.89-3.23). By 14 days, there were 2 deaths in the penicillin-gentamicin group, 3 in the ceftriaxone group and 11 in the TMP-SMX-gentamicin group [relative risk 5.58, 95% confidence interval: 1.26-24.72 (group 3 versus 1)]. When hospitalization of sick infants is unfeasible, outpatient therapy with injectable antibiotics is an effective option. Procaine penicillin-gentamicin was superior to TMP-SMX-gentamicin. Ceftriaxone is a more expensive option, and may be less effective, although this requires further research.

Selection of reference genes for real-time expression studies in Streptococcus agalactiae

Streptococcus agalactiae, group B streptococci (GBS) is the leading cause of severe bacterial infections in newborns. GBS expression studies allowed the identification and characterization of virulence factors and a better understanding of the host–pathogen–environment interactions. The measurement of transcript levels by quantitative real‐time PCR (qRT-PCR) is a widely used technique in GBS; however, a systematic evaluation and validation of reference gene stability for normalization purposes in GBS expression studies is currently lacking. Therefore, we analyzed the stability of 10 candidate reference genes (16SrRNA, glcK, glnA, groEL, gyrA, recA, rpoB, rpsL, sdhA and tkt) in three GBS prototype strains (O90R, NEM316 and 2603V/R) grown at different temperature conditions (37°C and 40°C). Our approach was based on the calibration of transcript levels from each gene against the number of bacteria from the same sample (ratio messenger RNA/genomic DNA). As a complementary analysis, reference gene stability was also investigated through the bioinformatic applications, geNorm and NormFinder. Considering the whole GBS development cycle, only a minority of genes were stable under both growth conditions, but this number increased when restricting the analysis to the logarithmic time-points. The range of stable genes was higher at 37°C, where recA and sdhA were stable simultaneously for the three strains, and six out of 10 genes were stable for at least two strains. At 40°C, recA showed up again as one of the best options, suggesting its potential use as reference gene in future qRT-PCR studies. The results generated with geNorm and NormFinder were consistent with those obtained experimentally and evidenced minor variations either among strains or temperature conditions.In conclusion, the fluctuation of expression of reference genes observed among different GBS strains and growth conditions highlights the importance of carefully validating, for each experimental scenario, the use of reference genes for qRT-PCR normalization purposes. Nevertheless, recA seems to be a good candidate for such optimizations.

Unexplained neonatal jaundice as an early diagnostic sign of urinary tract infection

Hyperbilirubinemia is one of the presenting signs of bacterial infection in newborns, and the association of neonatal jaundice with urinary tract infection (UTI) has been particularly emphasized. The aim of this study was to determine the prevalence of UTI in asymptomatic jaundiced neonates younger than 4 weeks old. We prospectively evaluated 120 asymptomatic jaundiced and 122 healthy neonates without jaundice younger than 4 weeks old for UTI. Patients with UTI, defined as >10,000 colony-forming units of a single pathogen per milliliter urine obtained by bladder catheterization, were evaluated for sepsis. Of 120 asymptomatic jaundiced neonates with a mean age of 7 ± 4 days, 15 (12.5%) had a UTI. Of 122 healthy neonates, positive urine cultures from a urine bag were found in eight cases; however on reevaluation, urine cultures from bladder catheterization were negative. The most common pathogen isolated from the UTI cases was Klebsiella pneumoniae. Also, unconjugated hyperbilirubinemia was detected in all jaundiced patients with UTI. UTI was found in 12.5% of the asymptomatic jaundiced neonates with the onset of unconjugated hyperbilirubinemia in the first week of life. Therefore, we suggest that urine culture should be considered as a part of the diagnostic evaluation of jaundiced neonates older than 3 days with an unexplained etiology.

A group B streptococcal pilus protein promotes phagocyte resistance and systemic virulence

Group B Streptococcus (GBS) is a major cause of invasive bacterial infections in newborns and certain adult populations. Surface filamentous appendages known as pili have been recently identified in GBS. However, little is known about the role of these structures in disease pathogenesis. In this study we sought to probe potential functional role(s) of PilB, the major GBS pilus protein subunit, by coupling analysis of an isogenic GBS pilB knockout strain with heterologous expression of the pilB gene in the nonpathogenic bacterium Lactococcus lactis. We found the knockout GBS strain that lacked PilB was more susceptible than wild-type (WT) GBS to killing by isolated macrophages and neutrophils. Survival was linked to the ability of PilB to mediate GBS resistance to cathelicidin antimicrobial peptides. Furthermore, the PilB-deficient GBS mutant was more readily cleared from the mouse bloodstream and less-virulent in vivo compared to the WT parent strain. Strikingly, overexpression of the pilB gene alone in L. lactis enhanced resistance to phagocyte killing, increased bloodstream survival, and conferred virulence in a mouse challenge model. Together these data demonstrate that the pilus backbone subunit, PilB, plays an integral role in GBS virulence and suggests a novel role for gram-positive pili in thwarting the innate defenses of phagocyte killing.

Beyond the complete blood cell count and C-reactive protein: a systematic review of modern diagnostic tests for neonatal sepsis.

To systematically review the accuracy of modern laboratory tests for the diagnosis of serious bacterial infection in newborns. The MEDLINE, EMBASE, and Cochrane Library databases were searched using the keywords newborn, infection, sepsis, and diagnosis. We included studies published from 1995 through 2001 that included infants younger than 90 days with proven bacterial growth in a sample from a sterile site. Whenever possible, relevant data were extracted to calculate likelihood ratios (LRs) for whether each test can diagnose a serious bacterial infection. Two independent reviewers selected and reviewed the articles (interobserver agreement, kappa = 0.80). All disagreements were resolved by consensus. Of the 137 citations we retrieved, 37 articles met the inclusion criteria; 17 studies, evaluating 11 different tests, met the highest methodological criteria. The most commonly evaluated test was interleukin 6 (IL-6) level (n = 7 studies). The remaining tests were each evaluated in no more than 3 studies. Positive LRs ranged from 1.5 to infinity. Six individual tests examined in 8 studies had LRs of more than 10 (range, 12.5- infinity ). Combined tests also had a wide range of LRs (3.4-9.9). All studies were performed in single medical centers and had small sample sizes, making recommendations according to gestational age criteria difficult. We found few methodologically rigorous studies of the accuracy of laboratory tests for the diagnosis of bacterial infection in newborns; in a significant proportion of studies, the accuracy of the tests could not be independently determined because of a lack of adequate data. There was marked heterogeneity in sample selection and cutoff levels for diagnosis of neonatal sepsis. A few tests showed promising accuracy, but there are insufficient data to support their confident use as clinical tools.