A meta-analysis was performed to evaluate the accuracy of determination of procalcitonin (PCT) and C-reactive protein (CRP) levels for the diagnosis of bacterial infection. The analysis included published studies that evaluated these markers for the diagnosis of bacterial infections in hospitalized patients. PCT level was more sensitive (88% [95% confidence interval [CI], 80%-93%] vs. 75% [95% CI, 62%-84%]) and more specific (81% [95% CI, 67%-90%] vs. 67% [95% CI, 56%-77%]) than CRP level for differentiating bacterial from noninfective causes of inflammation. The Q value for PCT markers was higher (0.82 vs. 0.73). The sensitivity for differentiating bacterial from viral infections was also higher for PCT markers (92% [95% CI, 86%-95%] vs. 86% [95% CI, 65%-95%]); the specificities were comparable (73% [95% CI, 42%-91%] vs. 70% [95% CI, 19%-96%]). The Q value was higher for PCT markers (0.89 vs. 0.83). PCT markers also had a higher positive likelihood ratio and lower negative likelihood ratio than did CRP markers in both groups. On the basis of this analysis, the diagnostic accuracy of PCT markers was higher than that of CRP markers among patients hospitalized for suspected bacterial infections.

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Serum Procalcitonin and C-Reactive Protein Levels as Markers of Bacterial Infection: A Systematic Review and Meta-analysis

To assess the diagnostic value of procalcitonin (PCT), interleukin (IL)-6, IL-8, and standard measurements in identifying critically ill patients with sepsis, we performed prospective measurements in 78 consecutive patients admitted with acute systemic inflammatory response syndrome (SIRS) and suspected infection. We estimated the relevance of the different parameters by using multivariable regression modeling, likelihood-ratio tests, and area under the receiver operating characteristic curves (AUC). The final diagnosis was SIRS in 18 patients, sepsis in 14, severe sepsis in 21, and septic shock in 25. PCT yielded the highest discriminative value, with an AUC of 0.92 (CI, 0.85 to 1.0), followed by IL-6 (0.75; CI, 0.63 to 0.87), and IL-8 (0.71; CI, 0.59 to 0.83; p < 0.001). At a cutoff of 1.1 ng/ml, PCT yielded a sensitivity of 97% and a specificity of 78% to differentiate patients with SIRS from those with sepsis-related conditions. Median PCT concentrations on admission (ng/ ml, range) were 0.6 (0 to 5.3) for SIRS; 3.5 (0.4 to 6.7) for sepsis; 6.2 (2.2 to 85) for severe sepsis; and 21.3 (1.2 to 654) for septic shock (p < 0.001). The addition of PCT to a model based solely on standard indicators improved the predictive power of detecting sepsis (likelihood ratio test; p = 0.001) and increased the AUC value for the routine value-based model from 0.77 (CI, 0.64 to 0.89) to 0.94 (CI, 0.89 to 0.99; p = 0.002). In contrast, no additive effect was seen for IL-6 (p = 0.56) or IL-8 (p = 0.14). Elevated PCT concentrations appear to be a promising indicator of sepsis in newly admitted, critically ill patients capable of complementing clinical signs and routine laboratory parameters suggestive of severe infection.

https://www.atsjournals.org/doi/pdf/10.1164/ajrccm.164.3.2009052

Diagnostic value of procalcitonin, interleukin-6, and interleukin-8 in critically ill patients admitted with suspected sepsis

One of the most challenging practical and daily problems in intensive care medicine is the interpretation of the results from diagnostic tests. In neonatology and pediatric intensive care the early diagnosis of potentially life-threatening infections is a particularly important issue. A plethora of tests have been suggested to improve diagnostic decision making in the clinical setting of infection which is a clinical example used in this article. Several criteria that are critical to evidence-based appraisal of published data are often not adhered to during the study or in reporting. To enhance the critical appraisal on articles on diagnostic tests we discuss various measures of test accuracy: sensitivity, specificity, receiver operating characteristic curves, positive and negative predictive values, likelihood ratios, pretest probability, posttest probability, and diagnostic odds ratio. We suggest the following minimal requirements for reporting on the diagnostic accuracy of tests: a plot of the raw data, multilevel likelihood ratios, the area under the receiver operating characteristic curve, and the cutoff yielding the highest discriminative ability. For critical appraisal it is mandatory to report confidence intervals for each of these measures. Moreover, to allow comparison to the readers' patient population authors should provide data on study population characteristics, in particular on the spectrum of diseases and illness severity.

/pdf/a-readers-guide-to-the-interpretation-of-diagnostic-test-1fn5q3v0kb.pdf

A readers' guide to the interpretation of diagnostic test properties: clinical example of sepsis.

The genital mycoplasmas represent a complex and unique group of microorganisms that have been associated with a wide array of infectious diseases in adults and infants. The lack of conclusive knowledge regarding the pathogenic potential of Mycoplasma and Ureaplasma spp. in many conditions is due to a general unfamiliarity of physicians and microbiology laboratories with their fastidious growth requirements, leading to difficulty in their detection; their high prevalence in healthy persons; the poor design of research studies attempting to base association with disease on the mere presence of the organisms in the lower urogenital tract; the failure to consider multifactorial aspects of diseases; and considering these genital mycoplasmas only as a last resort. The situation is now changing because of a greater appreciation of the genital mycoplasmas as perinatal pathogens and improvements in laboratory detection, particularly with regard to the development of powerful molecular nucleic acid amplification tests. This review summarizes the epidemiology of genital mycoplasmas as causes of neonatal infections and premature birth; evidence linking ureaplasmas with bronchopulmonary dysplasia; recent changes in the taxonomy of the genus Ureaplasma; the neonatal host response to mycoplasma and ureaplasma infections; advances in laboratory detection, including molecular methods; and therapeutic considerations for treatment of systemic diseases.

https://www.medica-tec.com/arg/files/ELITECH%20-%20Mycoplasmas%20and%20Ureaplasmas%20as%20Neonatal%20Pathogens%20-%20CLINICAL%20MICROBIOLOGY%20REVIEWS.pdf

Mycoplasmas and Ureaplasmas as Neonatal Pathogens

Objective:The use of procalcitonin (ProCT) as a marker of several clinical conditions, in particular, systemic inflammation, infection, and sepsis, will be clarified, and its current limitations will be delineated. In particular, the need for a more sensitive assay will be emphasized. For these purp

Procalcitonin assay in systemic inflammation, infection, and sepsis: clinical utility and limitations.

We evaluated the reliability of serum concentrations of procalcitonin for the diagnosis of early- and late-onset sepsis in a neonatal intensive care unit (NICU) setting. Timed procalcitonin determinations were prospectively obtained during two postnatal periods: 0-48 hours of age (period 1) and 3-30 days of age (period 2). In period 1, we measured procalcitonin concentrations in 83 healthy newborns (group 0) and in 120 NICU patients (14 with culture-proven sepsis, group 1A; 14 with clinical septicemia, group 1B; 75 with no evidence of infection, group 2; and 17 with uncertain findings, group 3). After we established 95% hour-specific reference ranges for group 0, we performed multiple linear regression analyses to determine which maternal, intrapartum, and neonatal complications would affect normal procalcitonin values. Maternal diabetes was the only variable identified in group 2 patients that induced a significant deviation from procalcitonin reference ranges. Analyses of the pooled procalcitonin values obtained for group 1 patients over the 48-hour period after birth yielded a sensitivity of 92.6% and a specificity of 97.5% for procalcitonin concentrations in the detection of early-onset sepsis. In period 2, blood samples from 23 cases with systemic infections were analyzed for procalcitonin concentrations at the onset of signs of infection. The control group was formed by matching four uninfected NICU patients to each infected case. None of the procalcitonin values for the 92 controls overlapped those for the cases (sensitivity and specificity, 100%). Procalcitonin is a promising marker for the diagnosis of early- and late-onset sepsis in neonates at high risk for this infection.

Reliability of Procalcitonin Concentrations for the Diagnosis of Sepsis in Critically Ill Neonates

OBJECTIVE To assess the utility of determining interleukin 6 (IL-6) concentrations for diagnosing early (< or = 48 h of life) and late onset infection in a neonatal intensive care setting. METHODS We measured serum IL-6 values in five groups of neonates on both postnatal Days 1 and 2 (early sampling): Group 1, patients with clinical and microbiologic evidence of early onset infection; Group 2, patients with negative body fluid cultures but strong evidence of infection (clinical septicemia); Group 3, patients without clinical and microbiologic evidence of infection; Group 4, patients in whom infection could be neither confirmed nor excluded; and Group 5, healthy neonates with a normal postnatal course. We also measured IL-6 values in older neonates who during their hospital stay developed systemic infection (late sampling). Three controls matched for duration of hospital stay and birth date were chosen for each patient. RESULTS On postnatal Day 1 IL-6 values were elevated in all four patient groups compared with those in healthy neonates (P < 0.05 by analysis of variance (ANOVA)). There were no significant differences found among patient groups. On postnatal Day 2 IL-6 concentrations were persistently elevated in Groups 1 and 2 compared with values from those in Group 3, Group 4 and healthy controls (P < 0.01). At this time no significant differences in IL-6 values were found between uninfected symptomatic patients (Group 3), patients with uncertain findings (Group 4) and healthy controls. IL-6 concentrations were significantly higher in patients with late onset infection at presentation than in the patient controls (P < 0.0001) and returned to low values in those who recovered from infection. CONCLUSIONS There are differences in the serum concentrations of IL-6 that can be helpful in detecting early and late onset infection in preterm and term neonates. During the first 48 h of life serial IL-6 determinations are necessary so as not to overdiagnose infection in a neonatal intensive care setting.

Interleukin 6 in neonates with early and late onset infection.

Background: The reported sensitivities and specificities of procalcitonin (PCT) concentrations for the diagnosis of neonatal infection vary widely. A postnatal increase of PCT has been observed in healthy term newborns with a peak at ≈24 h of age, and many questions remain regarding maternal and perinatal factors that may influence the normal PCT kinetics during the immediate postnatal period.

Methods: We prospectively investigated the association between the serum PCT values obtained from 121 mothers at delivery and serum PCT in their healthy, term offspring at birth as well as at 24 and 48 h of age. We also analyzed whether obstetric and perinatal factors would alter maternal and neonatal PCT response.

Results: PCT concentrations in the babies at birth were significantly higher than in the mothers ( P <0.0001), with even larger differences at 24 and 48 h of age. None of the variables identified from maternal and perinatal histories had a significant effect on maternal PCT response. In the healthy neonate, the variables that significantly affected the concentration of PCT at birth were the mothers’ PCT ( P <0.01), maternal group B streptococcus colonization ( P <0.05), and rupture of membranes ≥18 h ( P <0.01). The coefficient of linear correlation between the mother’s PCT concentration and that of the baby at birth was 0.32 ( P <0.01). The only variable that significantly altered the PCT concentration at both 24 ( P <0.01) and 48 ( P <0.01) h of age was rupture of membranes ≥18 h. Nonetheless, the PCT response observed during the 48-h period after birth among healthy babies born to mothers with risk factors for infection was well below that reported previously among age-matched neonates with sepsis.

Conclusions: The postnatal increase of PCT observed in the healthy neonate with peak values at 24 h of age most likely represents endogenous synthesis. In estimating the sensitivities and specificities of PCT for diagnosis of sepsis throughout the initial 48 h of life, it is important to consider the normal PCT kinetics and the pattern(s) of PCT response in the healthy neonate.

Serum procalcitonin concentrations in term delivering mothers and their healthy offspring: a longitudinal study.

Objective. To determine whether the presence of Ureaplasma urealyticum in the respiratory tracts of very low birth weight infants is associated with increased risk of pneumonia, radiographic evidence of severe bronchopulmonary dysplasia during the second or third week of life (precocious) and oxygen dependency at 36 weeks of corrected postnatal gestational age. Methods. From October, 1993, to January, 1996, all infants who met the following entry criteria were enrolled in the study: birth weights ≤1500 g; admission to the NICU within 24 h after birth; evidence on admission of respiratory distress; and no prior antibiotic treatment. Infants were cultured for mycoplasmas, viruses, chlamydiae and aerobic and anaerobic bacteria. Results. Ninety-four critically ill newborns constituted our study cohort. Within 7 days of birth more infants with U. urealyticum infection showed radiographic features of pneumonia (53.1%, 25 of 47) than infants without U. urealyticum infection (21.2%, 10 of 47). Infants with U. urealyticum were more likely to have radiographic evidence of precocious bronchopulmonary dysplasia than those without this isolate (22.5%, 9 of 40 vs. 2.3%, 1 of 42). The relative risk of oxygen dependency at 36 weeks of corrected age in U. urealyticum-positive infants was 11.0 times that in U. urealyticum-negative infants (95% confidence interval, 1.6 to 75.5). Association of U. urealyticum and chronic lung disease at this age was not weakened after adjustments were made in a multivariate analysis for other significant risk factors including gestational age and presence of a patent ductus arteriosus. Conclusions. Isolation of U. urealyticum from respiratory tracts is associated with radiographic changes compatible with pneumonia within 7 days of birth, precocious bronchopulmonary dysplasia and severe pulmonary outcome.

Ureaplasma urealyticum and pulmonary outcome in a neonatal intensive care population

The tracheal isolation of Ureaplasma urealyticum from critically ill infants was investigated to determine if the organism was associated with an inflammatory response. Twenty nine neonates consecutively admitted for acute respiratory disease, with birthweights of < 1301 g and no evidence of viral, chlamydial, or bacterial infections, were identified. Culture results for ureaplasmas were correlated with white cell counts and clinical and radiographic features. Sixteen infants had tracheal aspirates and/or blood specimens positive for U urealyticum. Pneumonia was diagnosed more frequently in the U urealyticum positive infants than in the 13 who were negative for the organism. The mean total white cell count, absolute neutrophil, and band form counts were significantly higher in the U urealyticum positive group than in the negative group. These data suggest that U urealyticum can induce an inflammatory response in selected individuals who present with clinical, radiographic, and, in some instances, histological features of pneumonia.

https://fn.bmj.com/content/fetalneonatal/73/1/F37.full.pdf

Naila Rossi

Papers

Reliability of Procalcitonin Concentrations for the Diagnosis of Sepsis in Critically Ill Neonates

Interleukin 6 in neonates with early and late onset infection.

Serum procalcitonin concentrations in term delivering mothers and their healthy offspring: a longitudinal study.

Ureaplasma urealyticum and pulmonary outcome in a neonatal intensive care population

Ureaplasma urealyticum as a cause of pneumonia in preterm infants: analysis of the white cell response.