pus was available for culture.) The results in Bristol further supported a impression that the phage type of the staphylococcus was related to the severity 01 infection. Thus the troublesome Phage Type 80 Staphylococcus which was n isolated in 1953 by Rountree and Freeman (1955) in Australia3 has enhanced virulen. and so infection with it leads to sloughs and tissue damage with considerable toxaetf1 t 0S A little boy was admitted with a partial-thickness burn of about twenty per cent^

Management of Sepsis.

C-reactive protein (CRP) is one of the most studied and most used laboratory tests for neonatal sepsis. As part of the acute-phase reaction to infection, it plays a central role in the humoral response to bacterial invasion. The delayed synthesis during the inflammatory response accounts for its low sensitivity during the early phases of the disease. Diagnostic accuracy clearly improves by the performance of serial determinations and by the combination with earlier markers such as interleukins or procalcitonin. CRP is as well particularly useful for monitoring the response to treatment and guiding antibiotic therapy, though nothing replaces the clinical impression and the gold standard (i.e. culture results). In spite of the large amount of research done on CRP in neonates, some topics are still not fully understood, such as the influence of noninfectious factors on CRP levels in healthy as well as in symptomatic neonates and the role of gestational age and birthweight on CRP kinetics. In this review, we aim to give an update on the current evidence on the use of CRP in neonates.

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An Update on the Use of C-Reactive Protein in Early-Onset Neonatal Sepsis: Current Insights and New Tasks

To evaluate the value of C-reactive protein and leukocyte indices in the workup of patients suspected of having infection in a neonatal intensive care setting, a literature search was conducted in all languages using MEDLINE (1966 to May, 1994), EMBASE (1988 to May, 1994), bibliographic lists of primary and review articles and personal files. Citations identified as potentially relevant were reviewed by two independent investigators; only studies meeting preset criteria for population, diagnostic test and data presentation were included. Two observers independently assessed studies using explicit methodologic criteria. All data from the articles were extracted by one observer, whereas the second reviewer checked these data for accuracy. Four of the selected studies dealt with leukocyte cunt and ratios. The chi sequare test for homogeneity of proportions revealed significant heterogeneity across studies (P = 0.014 for the ratios; P < 0.001 for white blood cell count), suggesting that test properties varied widely across studies. Fifteen of the selected studies evaluated C-reactive protein; of these six were qualitative using a latex agglutination method. Among these studies the chi sequare test for homogeneity of proportions was highly significant (P < 0.01), reflecting the great heterogeneity across studies. Among the nine studies that evaluated five different quantitative methods heterogeneity was agiain present (P < 0.001). Because of the striking heterogeneity among the studies evaluated, pooling to give a summary point estimate of the sensitivity and specificity of the various studies was not possible and the results are reported as ranges. Clinicians faced with a neonate with suspected sepsis cannot rely on either C-reactive protein or leukocyte indices alone to make a decision, given that the results vary significantly depending on the methods of measurement used and the target population.

Accuracy of leukocyte indices and C-reactive protein in the diagnosis of neonatal sepsis A critical review

Potential biomarkers for effective screening of neonatal sepsis infections: An overview.

Significant overtreatment with antibiotics for suspected early onset sepsis (EOS) constitutes a persisting clinical problem, generating unnecessary risks, harms, and costs for many newborns. We aimed to study feasibility and impact of a sepsis calculator to help guide antibiotic for suspected EOS in a European setting. In this single-center study, the sepsis calculator was implemented as an addition to and in accordance with existing protocols. One thousand eight hundred seventy-seven newborns ≥ 35 weeks of gestational age were prospectively evaluated; an analogous retrospective control group (n = 2076) was used for impact analysis. We found that empirical treatment with intravenous antibiotics for suspected EOS was reduced from 4.8 to 2.7% after sepsis calculator implementation (relative risk reduction 44% (95% confidence interval 21.4–59.5%)). No evidence for changes in time to treatment start, treatment duration, or proven sepsis rates was found. Adherence to sepsis calculator recommendation was 91%. Conclusion: Pragmatic and feasible implementation of the sepsis calculator yields a 44% reduction of empirical use of antibiotics for EOS, without signs of delay or prolongation of treatment. These findings warrant a multicenter, nation-wide, randomized study evaluating systematic use of the sepsis calculator prediction model and its effects in clinical practice outside of the USA.

Sepsis calculator implementation reduces empiric antibiotics for suspected early-onset sepsis.

Despite the advances in perinatal and neonatal care and use of newer potent antibiotics, the incidence of neonatal sepsis remains high and the outcome is still severe. For years, investigators have sought a test or panel of tests able to identify septic neonates accurately and rapidly in order to obtain an early diagnosis and develop a specific effective treatment for a successful outcome. In addition to the standard procedures (blood, CSF, and urine cultures), such panels have included a combination of haematological investigations (total, differential and immature cell counts), and levels of acute-phase reactants (principally CRP and procalcitonin), and cytokines (such as IL-6 or neutrophil CD64). Furthermore, the science of proteomics and genomics has been applied to the search for bio-markers, production of protein profiles and genetic polymorphisms that can rapidly help the prediction, early diagnosis, and treatment of human diseases, but, for now, data are as yet insufficient to confirm their validity.

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Cristina Loda

Papers

Laboratory aid to the diagnosis and therapy of infection in the neonate