Early identification of neonatal sepsis is a global issue because of limitations in diagnostic procedures. The objective of this study was to compare the diagnostic accuracy of neutrophil CD64 and C-reactive protein (CRP) as a single test for the early detection of neonatal sepsis.
A prospective study enrolled newborns with documented sepsis (n=11), clinical sepsis (n=12) and control newborns (n=14). CRP, neutrophil CD64, complete blood counts and blood culture were taken at the time of the suspected sepsis for the documented or clinical group and at the time of venipuncture for laboratory tests in control newborns. Neutrophil CD64 was analyzed by flow cytometry.
CD64 was significantly elevated in the groups with documented or clinical sepsis, whereas CRP was not significantly increased compared with controls. For documented sepsis, CD64 and CRP had a sensitivity of 91% and 9%, a specificity of 83% and 83%, a positive predictive value of 83% and 33% and a negative predictive value of 91% and 50%, respectively, with a cutoff value of 3.0 mg/dL for CD64 and 1.0 mg/dL for CRP. The area under the receiver-operating characteristic curves for CD64 index and CRP were 0.955 and 0.527 (P<0.01), respectively.
These preliminary data show that diagnostic accuracy of CD64 is superior to CRP when measured at the time of suspected sepsis, which implies that CD64 is a more reliable marker for the early identification of neonatal sepsis as a single determination compared with CRP.
Neutrophil CD64; C-reactive protein; Neonatal sepsis
Early onset bacterial sepsis is a feared complication of the newborn. A large proportion of infants admitted to the Neonatal Intensive Care Unit (NICU) for suspected sepsis receive treatment with potent systemic antibiotics while a diagnostic workup is in progress. The gold standard for detecting bacterial sepsis is blood culture. However, as pathogens in blood cultures are only detected in approximately 25% of patients, the sensitivity of blood culture is suspected to be low. Therefore, the diagnosis of sepsis is often based on the development of clinical signs, in combination with laboratory tests such as a rise in C – reactive protein (CRP). Molecular assays for the detection of bacterial DNA in the blood represent possible new diagnostic tools for early identification of a bacterial cause.
A broad range 16S rDNA polymerase chain reaction (PCR) without preincubation was compared to conventional diagnostic work up for clinical sepsis, including BACTEC blood culture, for early determination of bacterial sepsis in the newborn. In addition, the relationship between known risk factors, clinical signs, and laboratory parameters considered in clinical sepsis in the newborn were explored.
Forty-eight infants with suspected sepsis were included in this study. Thirty-one patients were diagnosed with sepsis, only 6 of these had a positive blood culture. 16S rDNA PCR analysis of blinded blood samples from the 48 infants revealed 10 samples positive for the presence of bacterial DNA. PCR failed to be positive in 2 samples from blood culture positive infants, and was positive in 1 sample where a diagnosis of a non-septic condition was established. Compared to blood culture the diagnosis of bacterial proven sepsis by PCR revealed a 66.7% sensitivity, 87.5% specificity, 95.4% positive and 75% negative predictive value. PCR combined with blood culture revealed bacteria in 35.1% of the patients diagnosed with sepsis. Irritability and feeding difficulties were the clinical signs most often observed in sepsis. CRP increased in the presence of bacterial infection.
There is a need for PCR as a method to quickly point out the infants with sepsis. However, uncertainty about a bacterial cause of sepsis was not reduced by the PCR result, reflecting that methodological improvements are required in order for DNA detection to replace or supplement traditional blood culture in diagnosis of bacterial sepsis.
Late-onset sepsis is responsible for high morbidity and mortality in newborn infants in the world and in particular in developing countries. In this study, we evaluated whether clinical characteristics, laboratory parameters and measurements of serum interleukin-8 (IL-8) are able to discriminate between late neonatal sepsis and normal baby.
This was a prospective (case-control) study conducted between March 2007 and April 2008, at the neonatal intensive care unit, Ghaem Hospital, Mashhad, Iran. The study comprised 93 neonates ≥72 hours of life. The infants were categorized in two groups based on the clinical presentation, and biochemical markers including complete blood count, C-reactive protein (CRP) and blood culture: 1) Control group including 42 infants with routine screening and 2) Case group consisting of 38 infants with definitive infection (positive blood and/or cerebrospinal fluid culture) or clinical sepsis (clinical and laboratory signs of infection without positive blood or CSF culture). Receiver-operating characteristic curves were used for the determination of thresholds for the infection group versus healthy neonate group.
Eighty infants were enrolled in this study. IL-8 and CRP decreased in order of definitive infection, clinical sepsis and healthy subjects respectively (P<0.001). Sensitivity, specificity, positive predictive value, negative predictive value for serum levels were 0.95, 0.1, 0.97, 0.1 for IL-8 and 0.83, 0.86, 0.83, 0.69 for CRP respectively (cut-off point for IL-8 >60pg/ml and for CRP>6mg/dl).
IL-8 may be a valid and early predictive marker of neonatal infection. Also, IL-8 is associated with severity of infection.
Interleukin-8; C-Reactive Protein; Sepsis; Newborn; Laboratory Marker
In the last few years, serum procalcitonin has been proposed as an early marker of infections in neonates, with varying results. In this study, we aimed to investigate the value of procalcitonin, and C- reactive protein in establishing the diagnosis of neonatal sepsis.
Materials and Methods
Blood samples were collected at admission from 69 neonates with suspected infection (admitted to the Neonatal Intensive Care Units at Alzahra and Dr Beheshti Hospital in and Fatema-Zahra in Najafabad from May 2005 to April 2006). Patients were categorized in different groups according to clinical symptoms of sepsis, bacteriological and laboratory results. Group I consisted of 20 newborns with positive blood cultures and other biological tests which suggested infection. Group II consisted of 49 neonates with negative blood cultures but had two or three of clinical signs of sepsis. The control group included 18 healthy neonates with physiological hyperbilirubinemia and no clinical and biological data of infection, referred to the hospital for bilirubin determination. Procalcitonin and C-reactive protein (CRP) were determined by immunoluminometric assay and nephlometry method respectively.
Mean levels of procalcitonin and CRP in septic neonates (group I) were significantly higher than the other two groups (P< 0.005). Sensitivity, specificity, positive predictive value and negative predictive value were determined for all markers and compared with each other.
We conclude that procalcitonin is a better marker than CRP in the diagnosis of neonatal sepsis.
C-reactive protein; Neonatal sepsis; Procalcitonin
Bacterial sepsis continues to be a major cause of morbidity and mortality in newborns. Bacterial pathogens of neonatal septicemia may vary from one country to another and within a country from one hospital or region to another. Both gram-negative and gram-positive bacteria are responsible in neonatal sepsis. This study was undertaken to determine the prevalent bacterial agents of neonatal sepsis and their antimicrobial susceptibility in a teaching hospital, Rasht, from February 2008 to February 2010.
This prospective study includes 611 newborns admitted with the probable diagnosis of septicemia. We studied the cases with positive blood culture, the pathogens and antibiotic resistance to different antibiotics.
Among 611 hospitalized newborns, 64 (10.6%) cases had positive blood culture. The commonest pathogens were Entrobacter (78.1%) and Klebsiella (6.2%).
According to the results, low birth weight and prematurity were associated with higher risk of sepsis significantly. The most common pathogen was Enterobacter. Treatment with effective antibiotics (e.g. gentamicin, cost effective and easily available) and hygienic care in the neonatal unit are recommended to eliminate the infectious factors especially Entrobacter.
Neonate; Sepsis; Antibiotics; Drug Resistance; Entrobacter; Bacterial Infection
Neonatal sepsis is a significant cause of morbidity and mortality in neonates. Appropriate clinical diagnosis and empirical treatment in a given setting is crucial as pathogens of bacterial sepsis and antibiotic sensitivity pattern can considerably vary in different settings. This study was conducted at Bugando Medical Centre (BMC), Tanzania to determine the prevalence of neonatal sepsis, predictors of positive blood culture, deaths and antimicrobial susceptibility, thus providing essential information to formulate a policy for management of neonatal sepsis.
This was a prospective cross sectional study involving 300 neonates admitted at BMC neonatal unit between March and November 2009. Standard data collection form was used to collect all demographic data and clinical characteristics of neonates. Blood culture was done on Brain Heart Infusion broth followed by identification of isolates using conventional methods and testing for their susceptibility to antimicrobial agents using the disc diffusion method.
Among 770 neonates admitted during the study period; 300 (38.9%) neonates were diagnosed to have neonatal sepsis by WHO criteria. Of 300 neonates with clinical neonatal sepsis 121(40%) and 179(60%) had early and late onset sepsis respectively. Positive blood culture was found in 57 (47.1%) and 92 (51.4%) among neonates with early and late onset neonatal sepsis respectively (p = 0.466). Predictors of positive blood culture in both early and late onset neonatal sepsis were inability to feed, lethargy, cyanosis, meconium stained liquor, premature rupture of the membrane and convulsion. About 49% of gram negatives isolates were resistant to third generation cephalosporins and 28% of Staphylococcus aureus were found to be Methicillin resistant Staphylococcus aureus (MRSA). Deaths occurred in 57 (19%) of neonates. Factors that predicted deaths were positive blood culture (p = 0.0001), gram negative sepsis (p = 0.0001) and infection with ESBL (p = 0.008) or MRSA (p = 0.008) isolates.
Our findings suggest that lethargy, convulsion, inability to feed, cyanosis, PROM and meconium stained liquor are significantly associated with positive blood culture in both early and late onset disease. Mortality and morbidity on neonatal sepsis is high at our setting and is significantly contributed by positive blood culture with multi-resistant gram negative bacteria.
The aim of this study was to determine whether maternal serum C-reactive protein (CRP) is of value in predicting funisitis and early-onset neonatal sepsis (EONS) in women with preterm labor or preterm premature rupture of membranes (PROM). This retrospective cohort study included 306 consecutive women with preterm labor or preterm PROM who delivered preterm singleton neonates (23-35 weeks gestation) within 72 hr of CRP measurement. The CRP level was measured with a highly sensitive immunoassay. The sensitivity, specificity, positive predictive value, and negative predictive value of an elevated serum CRP level (≥ 8 mg/L) were 74.1%, 67.5%, 32.8%, and 92.4% for funisitis, and 67.7%, 63.3%, 17.2%, and 94.6% for EONS, respectively. Logistic regression analysis demonstrated that elevated levels of serum CRP were significantly associated with funisitis and EONS, even after adjusting gestational age. The maternal serum CRP level obtained up to 72 hr before delivery is an independent predictor of funisitis and EONS in women with preterm labor or preterm PROM. A low serum CRP level (< 8 mg/L) has good negative predictive value in excluding funisitis and EONS, and may therefore be used as a non-invasive adjunct to clinical judgment to identify low-risk patients.
C-Reactive Protein; Early-Onset Neonatal Sepsis; Funisitis; Preterm Labor; Preterm Premature Rupture of Membrane
BACKGROUND: Infection in the neonatal period is an extremely serious condition and diagnosis is difficult. C-reactive protein (CRP) is widely used as a marker of infection; however, its usefulness is limited in the early phase. The role of soluble intracellular adhesion molecule-1 (sICAM-1), an adhesion molecule, has been examined in recent studies as an early marker of neonatal infection with controversial results. AIM: Assessment of sICAM-1 concentrations and correlation with CRP, which is the currently used marker of infection, in order to use sICAM as an early diagnostic tool in neonates suspected for infection METHODS: Blood samples and blood cultures were obtained from two groups of pre-term and full-term neonates with clinical suspicion of infection prior to the initiation of antibiotics. The sICAM-1 and CRP values were compared with the corresponding noninfected ones (n = 10 each). RESULTS: The sICAM-1 levels were found increased in the group of both premature and term neonates with infection compared with the corresponding healthy ones (P < 0.0001). Prematurity combined with infection resulted in excessive increase of the levels of sICAM-1 in comparison with full-term infected newborns (p < 0.001). CRP values were normal in all samples except one in both full-term and premature infected neonates on day 1 of clinically suspected infection. Serial detection of CRP values on days 2 and 4 of infection revealed a pattern according to which CRP values in premature neonates continued rising, while in the group of full terms these values, after rising on the second day, lowered on day 4. CONCLUSIONS: Increased sICAM-1 levels can be detected early in both full-term and premature neonates with sepsis while CRP levels are within normal range at the same time. Assessment of sICAM-1 concentrations may be used as a diagnostic tool in neonates suspected for infection, resulting in earlier initiation of antibiotic therapy and therefore improving their outcome.
The results of recent studies suggest the usefulness of PCT for early diagnosis of neonatal sepsis, with varying results. The aim of this prospective multicenter study was to determine the behavior of serum PCT concentrations in both uninfected and infected neonates, and to assess the value of this marker for diagnosis of neonatal sepsis of vertical transmission.
PCT was measured in 827 blood samples collected prospectively from 317 neonates admitted to 13 acute-care teaching hospitals in Spain over one year. Serum PCT concentrations were determined by a specific immunoluminometric assay. The diagnostic efficacy of PCT at birth and within 12–24 h and 36–48 h of life was evaluated calculating the sensitivity, specificity, and likelihood ratio of positive and negative results.
169 asymptomatic newborns and 148 symptomatic newborns (confirmed vertical sepsis: 31, vertical clinical sepsis: 38, non-infectious diseases: 79) were studied. In asymptomatic neonates, PCT values at 12–24 h were significantly higher than at birth and at 36–48 h of life. Resuscitation at birth and chorioamnionitis were independently associated to PCT values. Neonates with confirmed vertical sepsis showed significantly higher PCT values than those with clinical sepsis. PCT thresholds for the diagnosis of sepsis were 0.55 ng/mL at birth (sensitivity 75.4%, specificity 72.3%); 4.7 ng/mL within 12–24 h of life (sensitivity 73.8%, specificity 80.8%); and 1.7 ng/mL within 36–48 h of life (sensitivity 77.6%, specificity 79.2%).
Serum PCT was moderately useful for the detection of sepsis of vertical transmission, and its reliability as a maker of bacterial infection requires specific cutoff values for each evaluation point over the first 48 h of life.
Neonatal sepsis can be classified into two subtypes depending upon whether the onset of symptoms is before 72 hours of life (early-onset neonatal sepsis—EONS) or later (late-onset neonatal sepsis—LONS). These definitions have contributed greatly to diagnosis and treatment by identifying which microorganisms are likely to be responsible for sepsis during these periods and the expected outcomes of infection. This paper focuses on the tools that microbiologist can offer to diagnose and eventually prevent neonatal sepsis. Here, we discuss the advantages and limitation of the blood culture, the actual gold standard for sepsis diagnosis. In addition, we examine the utility of molecular techniques in the diagnosis and management of neonatal sepsis.
The aim of this study was to test the sensitivity and specificity of antigen detection for group B streptococcus (GBS) from the urine of neonates with early onset GBS sepsis. GBS sepsis was defined as early (< 48 hours) signs of sepsis in a neonate colonised with GBS. Neonates of 26 weeks' gestation or more, considered at risk for sepsis, were prospectively investigated for one year. Investigations included culture of superficial swabs to assess colonisation, blood culture, and the Wellcogen Strep B latex particle agglutination test on urine. Of 188 neonates investigated, 17 (9%) had GBS sepsis. The urine antigen test had a sensitivity of 88% and specificity of 98%. The positive predictive value was 79% and the negative predictive value 99%. Blood culture was positive in only five neonates (29%). The annual incidence of GBS sepsis was 4.0 per 1000 and of blood culture positive GBS disease was 1.2 per 1000 live births. Three neonates died. The application of the urine antigen test of clinical neonatal practice is discussed.
Aim. To determine serum IL-1β, IL-6, IL-8, and TNF-α levels in neonatal sepsis at the time of diagnosis and after therapy, and to show the meaningful on the follow up. Methods. This prospective study was performed on newborns who were hospitalized for neonatal sepsis and who were classified as culture-proven sepsis (n=12), as culture-negative sepsis (n=21), and as healthy newborns (n=17). Results. At the time of diagnosis, serum IL-1β, IL-6, IL-8, and TNF-α levels of culture-proven sepsis were significantly higher than those of the control groups (P<.05). At the time of diagnosis, IL-1β, IL-6, IL-8, and TNF-α levels of culture-proven sepsis and culture-negative sepsis were significantly higher than levels at the seventh day after antibiotic treatment. Conclusion. Serum IL-1β, IL-6, IL-8, and TNF-α are mediators of inflammation and can be used at the diagnosis and at the evaluation of the therapeutic efficiency in neonatal sepsis.
Manifestations of sepsis are sensitive but are poorly specific of infection. Our aim was to assess the value of daily measurements of C-reactive protein (CRP), temperature and white cell count (WCC) in the early identification of intensive care unit (ICU)-acquired infections.
We undertook a prospective observational cohort study (14 month). All patients admitted for ≥72 hours (n = 181) were divided into an infected (n = 35) and a noninfected group (n = 28). Infected patients had a documented ICU-acquired infection and were not receiving antibiotics for at least 5 days before diagnosis. Noninfected patients never received antibiotics and were discharged alive. The progression of CRP, temperature and WCC from day -5 to day 0 (day of infection diagnosis or of ICU discharge) was analyzed. Patients were divided into four patterns of CRP course according to a cutoff value for infection diagnosis of 8.7 mg/dl: pattern A, day 0 CRP >8.7 mg/dl and, in the previous days, at least once below the cutoff; pattern B, CRP always >8.7 mg/dl; pattern C, day 0 CRP ≤8.7 mg/dl and, in the previous days, at least once above the cutoff; and pattern D, CRP always ≤8.7 mg/dl.
CRP and the temperature time-course showed a significant increase in infected patients, whereas in noninfected it remained almost unchanged (P < 0.001 and P < 0.001, respectively). The area under the curve for the maximum daily CRP variation in infection prediction was 0.86 (95% confidence interval: 0.752–0.933). A maximum daily CRP variation >4.1 mg/dl was a good marker of infection prediction (sensitivity 92.1%, specificity 71.4%), and in combination with a CRP concentration >8.7 mg/dl the discriminative power increased even further (sensitivity 92.1%, specificity 82.1%). Infection was diagnosed in 92% and 90% of patients with patterns A and B, respectively, and in only two patients with patterns C and D (P < 0.001).
Daily CRP monitoring and the recognition of the CRP pattern could be useful in the prediction of ICU-acquired infections. Patients presenting maximum daily CRP variation >4.1 mg/dl plus a CRP level >8.7 mg/dl had an 88% risk of infection.
Neonatal sepsis is a major cause of morbidities and mortalities mostly remarkable in the third world nations.We aimed to assess the value of simultaneous measurement of procalcitonin (PCT) and interleukin-6 (IL-6) in association with high sensitive- C reactive protein(hs-CRP) in prediction of early neonatal sepsis.
A follow-up study was performed on 95 neonates who were below 12 hours (h) of age and had clinical signs of sepsis or maternal risk factors for sepsis. Neonates were assigned to 4 groups including “proven early-onset sepsis”, “clinical early-onset sepsis”, “negative infectious status”, and “uncertain infectious status”. Blood samples were obtained within the first 12 h of birth repeated between 24 hours and 36 hours of age for determination of serum levels of PCT, IL-6, hs-CRP, and white blood cell (WBC) count.
On admission, neonates with sepsis had a higher WBC count, IL-6, PCT, and hs-CRP levels compared with those neonates without sepsis. This remained significant even after 12–24 hours of admission. Also, patients with clinical evidences of sepsis had a higher serum level of PCT and IL-6 within 12–24 hours after admission compared to the patients with uncertain sepsis.
The combination of PCT and IL-6 yielded had a sensitivity of 88% and PCT and CRP (using the cutoff value of 8 mg/L) a sensitivity of 82%.The areas under the ROC curve for the two periods were 0.801, and 0.819 respectively.
In final The combination of IL-6, hs-CRP, and PCT seems to be predictive in diagnosis of early onset neonatal sepsis.
The organisms responsible for neonatal sepsis vary across geographical boundaries and with the time of illness thus periodic bacteriologic surveillance is a neccessity. The present study was therefore carried out to determine the common bacterial pathogens in Port Harcourt and their sensitivity pattern.
Four hundred and six neonates were prospectively screened for sepsis over a 6 month period. Sensitivity of the bacterial isolates to different antibiotics was determined using Kirby-Bauer diffusion method.
Gram negative organisms predominated (75.1%) with Klebsiella pneumonia (58.2%) being the commonest. The quinolones were the most sensitive antibiotics to the commonly isolated organisms.
Klebsiella pneumonia is the commonest organism responsible for neonatal sepsis in Port Harcourt. There is an overall decline in the antibiotic susceptibility to the commonly isolated bacterial pathogens.
Neonatal sepsis; Bacteria; Antibiotics; Port Harcourt
C-reactive protein (CRP) has been shown to be a valuable marker in the diagnosis of infection and in monitoring its response to antibiotics. Our objective was to evaluate serial CRP measurements after prescription of antibiotics to describe the clinical course of Community-Acquired Sepsis admitted to intensive care units (ICU).
During a 12-month period a multi-center, prospective, observational study was conducted, segregating adults with Community-Acquired Sepsis. Patients were followed-up during the first five ICU days, day of ICU discharge or death and hospital outcome. CRP-ratio was calculated in relation to Day 1 CRP concentration. Patients were classified according to the pattern of CRP-ratio response to antibiotics: fast response if Day 5 CRP-ratio was < 0.4, slow response if Day 5 CRP-ratio was between 0.4 and 0.8, and no response if Day 5 CRP-ratio was > 0.8. Comparison between survivors and non-survivors was performed.
A total of 891 patients (age 60 ± 17 yrs, hospital mortality 38%) were studied. There were no significant differences between the CRP of survivors and non-survivors until Day 2 of antibiotic therapy. On the following three days, CRP of survivors was significantly lower (P < 0.001). After adjusting for the Simplified Acute Physiology Score II and severity of sepsis, the CRP course was significantly associated with mortality (ORCRP-ratio = 1.03, confidence interval 95%= (1.02, 1.04), P < 0.001). The hospital mortality of patients with fast response, slow response and no response patterns was 23%, 30% and 41%, respectively (P = 0.001). No responders had a significant increase on the odds of death (OR = 2.5, CI95% = (1.6, 4.0), P < 0.001) when compared with fast responders.
Daily CRP measurements after antibiotic prescription were useful as early as Day 3 in identification of Community-Acquired Sepsis patients with poor outcome. The rate of CRP decline during the first five ICU days was markedly associated with prognosis. The identification of the pattern of CRP-ratio response was useful in the recognition of the individual clinical course.
C-reactive protein (CRP) is an indicator of inflammation, and is often used in the diagnosis of bacterial infections. It is poorly known whether CRP in bacterial infection is age-dependent.
Adult patients with a positive blood culture with E. coli or S. pneumoniae during 1994–2004 were included. CRP measured on the same date as the blood cultures were drawn (CRP1), 2–3 days (CRP2) and 4–7 days later (CRP3), were retrieved. The patients were divided into three age groups, < 65, 65–84, and ≥ 85, respectively. We studied three cut-off values for CRP and produced age-specific receiver operating characteristics (ROC) curves, using patients with acute coronary or cerebral infarction as controls.
890 patients and 421 controls were available. There was a statistically significant negative correlation between age and CRP1 – 0.072 (p = 0.032). The median CRP1 and CRP2 were significantly higher in the youngest age group. The area under the ROC-curve for the youngest age group was significantly greater than that of the two other age groups, but we found no statistically significant differences in sensitivity related to age. The diagnostic sensitivity of CRP was better for S. pneumoniae than for E. coli, 92.6% vs. 88.0% (p = 0.046) for a cut-off value of 40 mg/L, and 82.4% vs. 61.5% (p =< 0.01) for a cut-off value of 120 mg/L.
CRP is better in identifying infection with S. pneumoniae than with E. coli. We found a weakening of the CRP-response with age, but this is hardly of clinical significance.
Background. Sepsis is an important cause of mortality in newborns. However, a single reliable marker is not available for the diagnosis of neonatal late-onset sepsis (NLS). The aim of this study is to evaluate the value of serum amyloid A (SAA) and procalcitonin (PCT) in the diagnosis and follow-up of NLS. Methods. 36 septic and healthy newborns were included in the study. However, SAA, PCT, TNF-α, IL-1β, and CRP were serially measured on days 0, 4, and 8 in the patients and once in the controls.
Töllner's sepsis score (TSS) was calculated for each patient. Results. CRP, PCT, and TNF-α levels in septic neonates at each study day were significantly higher than in the controls (P = .001). SAA and IL-1β
levels did not differ from healthy neonates. The sensitivity and specificity were
86.8% and 97.2% for PCT, 83.3% and 80.6% for
TNF-α, 75% and 44.4% for SAA on day 0. Conclusion. Present study suggests that CRP seems to be the most helpful indicator and PCT and
TNF-α may be useful markers for the early diagnosis of NLS. However, SAA, IL-1β, and TSS are not reliable markers for the diagnosis and follow-up of NLS.
Neonatal sepsis is a major cause of neonatal mortality and morbidity. The current gold standard for diagnosis of sepsis, namely blood culture, suffers from low sensitivity and a reporting delay of approximately 48–72 h. Rapid detection of sepsis and institution of antimicrobial therapy may improve patient outcomes. Rapid and sensitive tests that can inform clinicians regarding the institution or optimization of antimicrobial therapy are urgently needed. The ideal diagnostic test should have adequate specificity and negative predictive value to reliably exclude sepsis and avoid unnecessary antibiotic therapy. We comprehensively searched for neonatal studies that evaluated molecular methods for diagnosis of sepsis. We identified 19 studies that were assessed with respect to assay methodology and diagnostic characteristics. In addition, we also reviewed newer molecular microbiological assays of relevance that have not been fully evaluated in neonates. Molecular methods offer distinct advantages over blood cultures, including increased sensitivity and rapid diagnosis. However, diagnostic accuracy and cost–effectiveness should be established before implementation in clinical practice.
diagnosis; FISH; microarray; molecular; neonate; PCR; sepsis
Neonatal sepsis can be divided into early onset, which is considered to be maternally acquired, and late onset, which is nosocomial in origin. Nosocomial sepsis is an important problem in neonatal nurseries and intensive care units. Studies from other nurseries in Malaysia have shown a high incidence and mortality from nosocomial sepsis.
The purpose of this study was to describe the incidence, aetiology and outcome of nosocomial bacterial sepsis in neonates admitted to the SCN of HKB and to describe the occurrence of nosocomial infection due to multiresistant organisms.
This prospective descriptive study was conducted from 1st February 1998 to 31st July 1998. In neonates suspected to have nosocomial sepsis, blood cultures were taken and the platelet count, total white cell count and C reactive protein level were determined. The empirical antibiotics given to the infant, the duration, and any changes made after culture results became available were recorded.
The nosocomial sepsis rate was 4.8 episodes per 100 babies admitted and the mortality rate was 24%. Multiresistant gram negative bacilli, MRSA and methicillin resistant coagulase negative staphylococci caused 46% of sepsis episodes.
The high incidence and mortality of nosocomial sepsis suggest that there is a need for an effective infection control program in the SCN.
Sepsis is the main cause of morbidity and mortality in intensive care units and its early diagnosis is not straightforward. Many studies have evaluated the usefulness of various markers of infection, including C-reactive protein (CRP), which is the most accessible and widely used. CRP is of weak diagnostic value because of its low specificity; a better understanding of patterns of CRP levels associated with a particular form of infection may improve its usefulness as a sepsis marker. In the present article, we apply multilevel modeling techniques and mixed linear models to CRP-related data to assess the time course of CRP blood levels in association with clinical outcome in children with different septic conditions.
We performed a retrospective analysis of 99 patients with systemic inflammatory response syndrome, sepsis, or septic shock who were admitted to the Pediatric Critical Care Unit at the University Hospital, Brno. CRP blood levels were monitored for 10 days following the onset of the septic condition. The effect of different septic conditions and of the surgical or nonsurgical diagnosis on CRP blood levels was statistically analyzed using mixed linear models with a multilevel modeling approach.
A significant effect of septic condition and diagnosis on the course of CRP levels was identified. In patients who did not progress to septic shock, CRP blood levels decreased rapidly after reaching peak values – in contrast to the values in patients with septic shock in whom CRP protein levels decreased slowly. Moreover, CRP levels in patients with a surgical diagnosis were higher than in patients with a nonsurgical condition. The magnitude of this additional elevation in surgical patients did not depend on the septic condition.
Understanding the pattern of change in levels of CRP associated with a particular condition may improve its diagnostic and prognostic value in children with sepsis.
We studied the usefulness of serum procalcitonin (PCT), interleukin-6 (IL-6), lipopolysaccharide binding protein (LBP) levels and C-reactive protein (CRP) levels, in differentiating between systemic inflammatory response syndrome (SIRS) and sepsis in critically ill patients. Methods. In this single centre prospective observational study we included all consecutive patients admitted with SIRS or sepsis to the ICU. Blood samples for measuring CRP, PCT, IL-6 and LBP were taken every day until ICU discharge. Results. A total of 76 patients were included, 32 with sepsis and 44 with SIRS. Patients with sepsis were sicker on admission and had a higher mortality. CRP, PCT, IL-6 and LBP levels were significantly higher in patients with sepsis as compared to SIRS. With PCT levels in the first 24 hours after ICU admission <2 ng/mL, sepsis was virtually excluded (negative predictive value 97%). With PCT >10 ng/mL, sepsis with bacterial infection was very likely (positive predictive value 88%). PCT was best at discriminating between SIRS and sepsis with the highest area under the ROC curve (0.95, 95% CI 0.90–0.99). Discussion. This study showed that PCT is more useful than LBP, CRP and IL-6 in differentiating sepsis from SIRS.
To diagnose catheter-related sepsis without removing the catheter, we evaluated the differential positivity times of cultures of blood drawn simultaneously from central venous catheter and peripheral sites. In a 450-bed cancer reference center, simultaneous central- and peripheral-blood cultures were prospectively performed for patients with suspicion of catheter-related sepsis over an 18-month period. Data for 64 patients for whom the same microorganisms were found when central- and peripheral-blood samples were cultured were retrospectively reviewed by two independent physicians blinded to the differential positivity time values in order to establish or refute the diagnosis of catheter-related sepsis. The diagnosis was established in 28 cases, refuted in 14, and indeterminate in the remaining 22. The differential positivity time was significantly greater for patients with catheter-related sepsis (P < 10−4). A cutoff limit of +120 min had 100% specificity and 96.4% sensitivity for the diagnosis of catheter-related sepsis. These results strongly suggest that measurement of the differential positivity time might be a reliable tool facilitating the diagnosis of catheter-related sepsis in patients with an indwelling catheter.
Diagnosis of neonatal infection is difficult, because of it's non-specific clinical presentation and the lack of reliable diagnostic tests. The purpose of this study was to examine the potential diagnostic value of serum soluble intercellular adhesion molecule-1 (sICAM-1), soluble E-selectin (sE-selectin), highly sensitive C-reactive protein (hsCRP) and serum amyloid A (SAA) measurements, both individually and in combination in the setting of a neonatal intensive care unit.
219 consecutive serum samples were taken from 149 infants undergoing sepsis work up in a neonatal intensive care unit. Clinical diagnosis was established in a prospective manner, blind to the results of the study measurements. Infants were classified by an experienced paediatrician as infected or not-infected, one week after presentation. Classification was based on clinical presentation, routine laboratory and radiological investigations and response to therapy. The infected group were sub-classified as (a) culture positive infection or (b) culture negative infection. sICAM-1, sE-selectin, hsCRP and SAA levels were determined from stored serum samples after diagnosis was established. Further sub-group analysis of results was undertaken according to early or late onset of infection and preterm or term status. Statistical analysis utilised Mann Whitney U test and ROC curve analysis.
There were significantly increased serum levels of sICAM-1, hsCRP, E selectin (p < 0.001) and SAA (p = 0.004) in infected infants compared with non-infected. ROC curve analysis indicated area under the curve values of 0.79 (sICAM-1), 0.73 (hsCRP), 0.72 (sE-selectin) and 0.61 (SAA). ROC curve analysis also defined optimum diagnostic cut-off levels for each measurement. The performance characteristics of sICAM-1, hsCRP and sE-selectin included a high negative predictive value (NPV) for culture positive infection and this was enhanced by combination of all 4 measurements. Clinical subgroup analysis suggested particularly high NPV for early onset symptoms, however further studies are required to elucidate this finding.
All four study measurements demonstrated some diagnostic value for neonatal infection however sICAM-1, hsCRP and sE-selectin demonstrated the highest NPV individually. The optimum diagnostic cut off level for hsCRP measurement in this study was much lower than currently used in routine clinical practice. Use of a combination of measurements enhanced diagnostic performance, demonstrating sensitivity of 90.3% and NPV of 91.3%. This study suggests there may be value in use of several of these markers, individually and in combination to assist in excluding neonatal infection. Further work is needed to confirm a specific role in the exclusion of early onset infection.
Objective: To investigate the spectrum of organisms causing neonatal sepsis in Peshawar, Pakistan and to assess their sensitivity to various groups of drugs.
Methods: Blood taken from newborn babies admitted to the special care baby unit at the Khyber Teaching Hospital with a clinical diagnosis of neonatal sepsis was cultured. The data obtained from October 1997 to December 2000 were analysed and the results tabulated.
Results: A total of 1598 blood cultures were taken; 1003 were positive (positivity rate 62.8%). Escherichia coli was the most common organism found (36.6%), followed by Staphylococcus aureus (29.5%), Pseudomonas (22.4%), Klebsiella (7.6%), and Proteus (3.8%). No group B streptococcus was grown. Listeria monocytogenes was found in one cerebrospinal fluid culture. E coli and Pseudomonas showed a high degree of resistance to commonly used antibiotics (ampicillin, augmentin, and gentamicin), a moderate degree of resistance to cephalosporin (cefotaxime, ceftzidime, and ceftrioxone), and low resistance to drugs not used for newborn babies (ofloxacin, ciprofloxacin, and enoxabid). S aureus showed a low resistance to all three groups of antibiotics.
Conclusion: Neonatal sepsis remains one of the leading causes of neonatal admission, morbidity, and mortality in developing countries. Gram negative organisms are the major cause of neonatal sepsis in Peshawar. Such organisms have developed multidrug resistance, and management of patients infected with them is becoming a problem in developing countries.