TY - JOUR
AU - Behera,, Bijaylaxmi
AB - Abstract Objective To determine the time to normalization of procalcitonin (PCT) levels and duration of antibiotics in neonatal sepsis. Methods A prospective observational study design was used. The participants included were neonates with sepsis. The primary outcome measure was time to normalization of PCT levels and duration of antibiotics following clinical resolution. Results Time to normalization of PCT levels was 9.6 ± 4.2 days in neonates with septic shock, 6.2 ± 2.5 days in neonates without shock, 9.6 ± 3.1 days in neonates with culture-positive sepsis and 6.4 ± 3.1 days in neonates with culture-negative sepsis. Time to normalization of PCT levels according to the stage of systemic inflammatory response syndrome was 5.8 ± 2.8 days in neonates with sepsis, 6.1 ± 3.1 days in those with sepsis syndrome, 6.3 ± 3.3 days in those with early septic shock and 9.4 ± 3.6 days in those with multiorgan dysfunction syndrome. There was no morbidity and mortality in any neonate in the 4-week follow-up. Conclusion The duration of antibiotics can be determined by observing the time to normalization of PCT following clinical resolution of sepsis. neonatal sepsis, procalcitonin, duration of antibiotics, septic shock, culture-positive sepsis Although recent studies in adults with sepsis have suggested the utility of procalcitonin (PCT) for deciding the duration of antibiotic therapy by observing time to normalization of PCT levels, serial estimation of PCT levels in neonatal sepsis has been done in only few studies [1–10], while the estimation of time to normalization of PCT levels in neonatal sepsis has not been done. As time to normalization of PCT levels following clinical resolution is useful to decide the optimum duration of antibiotics in neonatal sepsis, its implication in antibiotic stewardship is remarkable. This prompted us to undertake the present study with the objective of determining time to normalization of PCT levels following clinical resolution of symptoms and duration of antibiotics in neonatal sepsis with special reference to blood culture positivity and presence of septic shock. METHODS The study was conducted on the neonates admitted to the Referral Neonatal Unit of a tertiary teaching hospital that caters exclusively to out-born neonates referred from community hospitals or brought from home by parents. A prospective study design approved by the Ethical Committee of the institution was used and written informed consent was obtained from the parents. Sick neonates of >34 weeks of gestation admitted between March 2016 and April 2017 with BOTH clinical features of sepsis AND positive bedside markers of sepsis were enrolled. Neonates with life-threatening congenital malformations, meningitis and prior exposure to antibiotics in the past 72 h were excluded from the study. It was estimated that a sample size of 81 neonates was required for the resulting estimate to fall within 10% of the true proportion with 95% confidence. To account for attrition, we intended to enrol 98 neonates. The clinical features of sepsis included any one of the following: poor feeding, lethargy, poor neonatal reflexes, hypothermia or hyperthermia, abdominal distention, respiratory distress, tachycardia and poor perfusion. Positive bedside markers of sepsis were abnormal total leukocyte count of >20 000/cu.mm or <5000/cu.mm, immature/total neutrophil count ratio >0.2, elevated micro-erythrocyte sedimentation rate (age in days + 2 mm/h in ≤14-day-old neonates or ≥15 mm/h), elevated C-reactive protein (CRP) of >1 mg/dl and elevated PCT levels. Clinical assessment of SIRS and its severity and progression was based on definitions suggested by Sáez-Llorens and McCracken [11]. Early-onset sepsis was defined as onset of sepsis at ≤72 h of age, and late onset was defined as onset of sepsis at >72 h of age. Clinical resolution was defined as complete absence of the presenting complaints and normal clinical examination. Assessment of PCT levels was repeated at clinical resolution, and if the levels did not normalize, then PCT levels were assessed every 48 h till normalization. PCT levels were known to the treating physicians, and antibiotics were stopped when the neonate was asymptomatic and subsequent PCT levels had normalized. PCT and CRP values were analysed using the QDx Instacheck Reader (Boditech Med Inc., Gang-won-do, Korea). Interpretation of PCT values is based on age-specific reference range according to Cheisa et al. [2]. At discharge, the danger signs of sepsis were explained to the parents; in case they observed any of the signs described, parents were instructed to report to the hospital. After discharge, the neonates were followed up weekly for up to 4 weeks of enrolment, to look for recurrence of symptoms or any morbidity. Telephonic contact details were obtained and used when required; there was no loss to follow-up. Statistical analysis was done using the software version SPSS 23.0. The differences between groups were analysed using independent t-tests for parametric data. Nonparametric data were analysed using Mann–Whitney U test. Pearson chi-square test and Fisher exact test were used for categorical variables. RESULTS The study flow is depicted in Fig. 1. Table 1 shows the baseline characteristics of the study population. Table 2 shows the time to resolution in 84 survivors. Time to normalization of PCT levels, resolution of symptoms, duration of antibiotics and duration of stay in hospital were significantly higher in the neonates with shock than in those without shock. Similarly, time to normalization of PCT levels, resolution of symptoms, duration of antibiotics and duration of stay in hospital were significantly higher in the neonates with culture-positive sepsis than in those with culture-negative sepsis. Fig.1. Open in new tabDownload slide Study flow. Fig.1. Open in new tabDownload slide Study flow. Table 1 Baseline characteristics of the study population (N = 98) Variable N (% age) Gestational age (mean ± SD) 38.1 ± 1.5 <37 weeks 11 (11.2) Birth weight (mean ± SD) 2523 ± 509 <2500 g 40 (40.8) SGA 25 (23.5) Male 69 (70.4) Age at admission in days (mean ± SD) 8.9 ± 7.4 Admission weight in grams (mean ± SD) 2454 ± 496 Admission length in centimetres (mean ± SD) 47.98 ± 2.91 Admission head circumference in centimetres (mean ± SD) 33.34 ± 2.25 Mean PCT at enrolment 7.64 ± 10.79 Variable N (% age) Gestational age (mean ± SD) 38.1 ± 1.5 <37 weeks 11 (11.2) Birth weight (mean ± SD) 2523 ± 509 <2500 g 40 (40.8) SGA 25 (23.5) Male 69 (70.4) Age at admission in days (mean ± SD) 8.9 ± 7.4 Admission weight in grams (mean ± SD) 2454 ± 496 Admission length in centimetres (mean ± SD) 47.98 ± 2.91 Admission head circumference in centimetres (mean ± SD) 33.34 ± 2.25 Mean PCT at enrolment 7.64 ± 10.79 SGA, Small for Gestational Age; SIRS, Systemic Inflammatory Response Syndrome; IQR, Inter Quartile Range. Open in new tab Table 1 Baseline characteristics of the study population (N = 98) Variable N (% age) Gestational age (mean ± SD) 38.1 ± 1.5 <37 weeks 11 (11.2) Birth weight (mean ± SD) 2523 ± 509 <2500 g 40 (40.8) SGA 25 (23.5) Male 69 (70.4) Age at admission in days (mean ± SD) 8.9 ± 7.4 Admission weight in grams (mean ± SD) 2454 ± 496 Admission length in centimetres (mean ± SD) 47.98 ± 2.91 Admission head circumference in centimetres (mean ± SD) 33.34 ± 2.25 Mean PCT at enrolment 7.64 ± 10.79 Variable N (% age) Gestational age (mean ± SD) 38.1 ± 1.5 <37 weeks 11 (11.2) Birth weight (mean ± SD) 2523 ± 509 <2500 g 40 (40.8) SGA 25 (23.5) Male 69 (70.4) Age at admission in days (mean ± SD) 8.9 ± 7.4 Admission weight in grams (mean ± SD) 2454 ± 496 Admission length in centimetres (mean ± SD) 47.98 ± 2.91 Admission head circumference in centimetres (mean ± SD) 33.34 ± 2.25 Mean PCT at enrolment 7.64 ± 10.79 SGA, Small for Gestational Age; SIRS, Systemic Inflammatory Response Syndrome; IQR, Inter Quartile Range. Open in new tab Table 2 Time to clinical resolution and normalization of PCT among survivors (N = 84) Variable All survivors Neonates with shock Neonates without shock Culture-positive cases Culture-negative cases Early-onset sepsis Late-onset sepsis N = 84 N = 15 N = 69 N = 11 N = 73 N = 31 N = 53 Resolution of symptoms in days 6.3 ± 2.9 8.9 ± 4.3* 5.7 ± 4.9* 7.7 ± 3.6# 6.1 ± 2.8# 7.2 ± 3.4$ 5.7 ± 2.6$ (mean ±SD) Median(IQR) 5 (4–7) 7 (5.5–10.5) 5 (4–6) 6 (5.5–9) 5 (4–7) 6 (4.2–10) 5 (4–6) Time to normalization of PCT in days 6.8 ± 3.1 9.6 ± 4.2& 6.2 ± 2.5& 9.6 ± 3.1+ 6.4 ± 3.1+ 7.5 ± 3.5** 6.4 ± 2.8** (mean ± SD) Median (IQR) 6 (4–7) 8 (7–10.5) 5 (4–7) 9 (8.5–10) 5 (4–7) 6.5 (4.3–10) 5 (4–7) Duration of antibiotics in days 7.2 ± 3.4 10.1 ± 4.6## 6.6 ± 3.1## 12.3 ± 3.4$$ 6.4 ± 3.1$$ 7.8 ± 3.9&& 6.9 ± 3.4&& (mean ± SD) Median (IQR) 6 (4–7) 8 (7–11.5) 5 (4–7) 12 (10–14) 5 (4–7) 7 (4.5–10) 5 (4–8) Duration of stay in days 7.2 ± 3.4 10.1 ± 4.6++ 6.6 ± 3.1++ 12.3 ± 3.4*** 6.4 ± 3.1*** 7.8 ± 3.9### 6.9 ± 3.4### (mean ± SD) Median (IQR) 6 (4–7) 8 (7–11.5) 5 (4–7) 12 (10–14) 5 (4–7) 7 (4.5–10) 5 (4–8) Variable All survivors Neonates with shock Neonates without shock Culture-positive cases Culture-negative cases Early-onset sepsis Late-onset sepsis N = 84 N = 15 N = 69 N = 11 N = 73 N = 31 N = 53 Resolution of symptoms in days 6.3 ± 2.9 8.9 ± 4.3* 5.7 ± 4.9* 7.7 ± 3.6# 6.1 ± 2.8# 7.2 ± 3.4$ 5.7 ± 2.6$ (mean ±SD) Median(IQR) 5 (4–7) 7 (5.5–10.5) 5 (4–6) 6 (5.5–9) 5 (4–7) 6 (4.2–10) 5 (4–6) Time to normalization of PCT in days 6.8 ± 3.1 9.6 ± 4.2& 6.2 ± 2.5& 9.6 ± 3.1+ 6.4 ± 3.1+ 7.5 ± 3.5** 6.4 ± 2.8** (mean ± SD) Median (IQR) 6 (4–7) 8 (7–10.5) 5 (4–7) 9 (8.5–10) 5 (4–7) 6.5 (4.3–10) 5 (4–7) Duration of antibiotics in days 7.2 ± 3.4 10.1 ± 4.6## 6.6 ± 3.1## 12.3 ± 3.4$$ 6.4 ± 3.1$$ 7.8 ± 3.9&& 6.9 ± 3.4&& (mean ± SD) Median (IQR) 6 (4–7) 8 (7–11.5) 5 (4–7) 12 (10–14) 5 (4–7) 7 (4.5–10) 5 (4–8) Duration of stay in days 7.2 ± 3.4 10.1 ± 4.6++ 6.6 ± 3.1++ 12.3 ± 3.4*** 6.4 ± 3.1*** 7.8 ± 3.9### 6.9 ± 3.4### (mean ± SD) Median (IQR) 6 (4–7) 8 (7–11.5) 5 (4–7) 12 (10–14) 5 (4–7) 7 (4.5–10) 5 (4–8) Note: p value (Mann–Whitney U test) = * 0.020; # 0.04; $ 0.02; & 0.0001; + 0.001; ** 0.11; ## 0.0006; $$ 0.0001; && 0.27; ++ 0.0006; *** 0.0001; ### 0.27. Open in new tab Table 2 Time to clinical resolution and normalization of PCT among survivors (N = 84) Variable All survivors Neonates with shock Neonates without shock Culture-positive cases Culture-negative cases Early-onset sepsis Late-onset sepsis N = 84 N = 15 N = 69 N = 11 N = 73 N = 31 N = 53 Resolution of symptoms in days 6.3 ± 2.9 8.9 ± 4.3* 5.7 ± 4.9* 7.7 ± 3.6# 6.1 ± 2.8# 7.2 ± 3.4$ 5.7 ± 2.6$ (mean ±SD) Median(IQR) 5 (4–7) 7 (5.5–10.5) 5 (4–6) 6 (5.5–9) 5 (4–7) 6 (4.2–10) 5 (4–6) Time to normalization of PCT in days 6.8 ± 3.1 9.6 ± 4.2& 6.2 ± 2.5& 9.6 ± 3.1+ 6.4 ± 3.1+ 7.5 ± 3.5** 6.4 ± 2.8** (mean ± SD) Median (IQR) 6 (4–7) 8 (7–10.5) 5 (4–7) 9 (8.5–10) 5 (4–7) 6.5 (4.3–10) 5 (4–7) Duration of antibiotics in days 7.2 ± 3.4 10.1 ± 4.6## 6.6 ± 3.1## 12.3 ± 3.4$$ 6.4 ± 3.1$$ 7.8 ± 3.9&& 6.9 ± 3.4&& (mean ± SD) Median (IQR) 6 (4–7) 8 (7–11.5) 5 (4–7) 12 (10–14) 5 (4–7) 7 (4.5–10) 5 (4–8) Duration of stay in days 7.2 ± 3.4 10.1 ± 4.6++ 6.6 ± 3.1++ 12.3 ± 3.4*** 6.4 ± 3.1*** 7.8 ± 3.9### 6.9 ± 3.4### (mean ± SD) Median (IQR) 6 (4–7) 8 (7–11.5) 5 (4–7) 12 (10–14) 5 (4–7) 7 (4.5–10) 5 (4–8) Variable All survivors Neonates with shock Neonates without shock Culture-positive cases Culture-negative cases Early-onset sepsis Late-onset sepsis N = 84 N = 15 N = 69 N = 11 N = 73 N = 31 N = 53 Resolution of symptoms in days 6.3 ± 2.9 8.9 ± 4.3* 5.7 ± 4.9* 7.7 ± 3.6# 6.1 ± 2.8# 7.2 ± 3.4$ 5.7 ± 2.6$ (mean ±SD) Median(IQR) 5 (4–7) 7 (5.5–10.5) 5 (4–6) 6 (5.5–9) 5 (4–7) 6 (4.2–10) 5 (4–6) Time to normalization of PCT in days 6.8 ± 3.1 9.6 ± 4.2& 6.2 ± 2.5& 9.6 ± 3.1+ 6.4 ± 3.1+ 7.5 ± 3.5** 6.4 ± 2.8** (mean ± SD) Median (IQR) 6 (4–7) 8 (7–10.5) 5 (4–7) 9 (8.5–10) 5 (4–7) 6.5 (4.3–10) 5 (4–7) Duration of antibiotics in days 7.2 ± 3.4 10.1 ± 4.6## 6.6 ± 3.1## 12.3 ± 3.4$$ 6.4 ± 3.1$$ 7.8 ± 3.9&& 6.9 ± 3.4&& (mean ± SD) Median (IQR) 6 (4–7) 8 (7–11.5) 5 (4–7) 12 (10–14) 5 (4–7) 7 (4.5–10) 5 (4–8) Duration of stay in days 7.2 ± 3.4 10.1 ± 4.6++ 6.6 ± 3.1++ 12.3 ± 3.4*** 6.4 ± 3.1*** 7.8 ± 3.9### 6.9 ± 3.4### (mean ± SD) Median (IQR) 6 (4–7) 8 (7–11.5) 5 (4–7) 12 (10–14) 5 (4–7) 7 (4.5–10) 5 (4–8) Note: p value (Mann–Whitney U test) = * 0.020; # 0.04; $ 0.02; & 0.0001; + 0.001; ** 0.11; ## 0.0006; $$ 0.0001; && 0.27; ++ 0.0006; *** 0.0001; ### 0.27. Open in new tab One patient with sepsis syndrome, 1 with early septic shock and 12 with refractory shock and multiorgan dysfunction syndrome (MODS) expired. All the neonates with refractory septic shock were also associated with MODS. Table 3 shows the time to resolution with reference to systemic inflammatory response syndrome. Time to normalization of PCT levels, resolution of symptoms, duration of antibiotics and duration of stay in hospital were significantly higher in the neonates with refractory shock with MODS than in those with sepsis and sepsis syndrome. Table 4 shows the recommended duration of antibiotics based on normalization of PCT values in our study (Fig. 2). Fig. 2. Open in new tabDownload slide Mean time to normalization of PCT levels in the study population. Fig. 2. Open in new tabDownload slide Mean time to normalization of PCT levels in the study population. Table 3 Time to resolution in survivors with reference to stages of SIRS Variable Sepsis Sepsis syndrome Early septic shock Refractory shock with MODS N = 31 N = 39 N = 8 N = 6 Resolution of symptoms in days 5.1 ± 1.9* 5.7 ± 1.4# 5.8 ± 1.5$ 8.9 ± 3.8& (mean ± SD)* 6 (5–7) 8.5 (5.75–11.75) 7 (6.5–10.5) Median(IQR) 4.5 (4–5.25) Time to normalization of PCT in 5.8 ± 2.6+ 6.1 ± 3.1** 6.3 ± 3.3## 9.4 ± 3.6$$ days (mean ± SD) 5 (4–6.25) 6 (5–7.25) 9.5 (7.75–11.75) 10 (7–10.5) Median (IQR) Duration of antibiotics in days 6.2 ± 3.3&& 6.4 ± 3.9++ 7 ± 3.5*** 9.4 ± 3.6### (mean ± SD)** 5 (4–7) 6 (5–7.75) 11 (7.75–13.5) 10 (7.5–10.5) Median (IQR) Duration of stay in neonates in days 6.2 ± 3.2$$$ 6.4 ± 3.9&&& 7 ± 3.5 9.4 ± 3.6+++ (mean ±SD)** 5 (4–7) 6 (5–7.75) 11 (7.75–13.75) 10 (7.5–10.5) Median (IQR) Variable Sepsis Sepsis syndrome Early septic shock Refractory shock with MODS N = 31 N = 39 N = 8 N = 6 Resolution of symptoms in days 5.1 ± 1.9* 5.7 ± 1.4# 5.8 ± 1.5$ 8.9 ± 3.8& (mean ± SD)* 6 (5–7) 8.5 (5.75–11.75) 7 (6.5–10.5) Median(IQR) 4.5 (4–5.25) Time to normalization of PCT in 5.8 ± 2.6+ 6.1 ± 3.1** 6.3 ± 3.3## 9.4 ± 3.6$$ days (mean ± SD) 5 (4–6.25) 6 (5–7.25) 9.5 (7.75–11.75) 10 (7–10.5) Median (IQR) Duration of antibiotics in days 6.2 ± 3.3&& 6.4 ± 3.9++ 7 ± 3.5*** 9.4 ± 3.6### (mean ± SD)** 5 (4–7) 6 (5–7.75) 11 (7.75–13.5) 10 (7.5–10.5) Median (IQR) Duration of stay in neonates in days 6.2 ± 3.2$$$ 6.4 ± 3.9&&& 7 ± 3.5 9.4 ± 3.6+++ (mean ±SD)** 5 (4–7) 6 (5–7.75) 11 (7.75–13.75) 10 (7.5–10.5) Median (IQR) Note: p value (Mann–Whitney U test): * versus & 0.006, # versus & 0.0003, $ versus & 0.05; + versus $$ 0.003, ** versus $$ 0.015, ## versus $$ 0.09, && versus ### 0.02; ++ versus ### 0.05; $$$ versus +++ 0.02, &&& versus +++ 0.05. Open in new tab Table 3 Time to resolution in survivors with reference to stages of SIRS Variable Sepsis Sepsis syndrome Early septic shock Refractory shock with MODS N = 31 N = 39 N = 8 N = 6 Resolution of symptoms in days 5.1 ± 1.9* 5.7 ± 1.4# 5.8 ± 1.5$ 8.9 ± 3.8& (mean ± SD)* 6 (5–7) 8.5 (5.75–11.75) 7 (6.5–10.5) Median(IQR) 4.5 (4–5.25) Time to normalization of PCT in 5.8 ± 2.6+ 6.1 ± 3.1** 6.3 ± 3.3## 9.4 ± 3.6$$ days (mean ± SD) 5 (4–6.25) 6 (5–7.25) 9.5 (7.75–11.75) 10 (7–10.5) Median (IQR) Duration of antibiotics in days 6.2 ± 3.3&& 6.4 ± 3.9++ 7 ± 3.5*** 9.4 ± 3.6### (mean ± SD)** 5 (4–7) 6 (5–7.75) 11 (7.75–13.5) 10 (7.5–10.5) Median (IQR) Duration of stay in neonates in days 6.2 ± 3.2$$$ 6.4 ± 3.9&&& 7 ± 3.5 9.4 ± 3.6+++ (mean ±SD)** 5 (4–7) 6 (5–7.75) 11 (7.75–13.75) 10 (7.5–10.5) Median (IQR) Variable Sepsis Sepsis syndrome Early septic shock Refractory shock with MODS N = 31 N = 39 N = 8 N = 6 Resolution of symptoms in days 5.1 ± 1.9* 5.7 ± 1.4# 5.8 ± 1.5$ 8.9 ± 3.8& (mean ± SD)* 6 (5–7) 8.5 (5.75–11.75) 7 (6.5–10.5) Median(IQR) 4.5 (4–5.25) Time to normalization of PCT in 5.8 ± 2.6+ 6.1 ± 3.1** 6.3 ± 3.3## 9.4 ± 3.6$$ days (mean ± SD) 5 (4–6.25) 6 (5–7.25) 9.5 (7.75–11.75) 10 (7–10.5) Median (IQR) Duration of antibiotics in days 6.2 ± 3.3&& 6.4 ± 3.9++ 7 ± 3.5*** 9.4 ± 3.6### (mean ± SD)** 5 (4–7) 6 (5–7.75) 11 (7.75–13.5) 10 (7.5–10.5) Median (IQR) Duration of stay in neonates in days 6.2 ± 3.2$$$ 6.4 ± 3.9&&& 7 ± 3.5 9.4 ± 3.6+++ (mean ±SD)** 5 (4–7) 6 (5–7.75) 11 (7.75–13.75) 10 (7.5–10.5) Median (IQR) Note: p value (Mann–Whitney U test): * versus & 0.006, # versus & 0.0003, $ versus & 0.05; + versus $$ 0.003, ** versus $$ 0.015, ## versus $$ 0.09, && versus ### 0.02; ++ versus ### 0.05; $$$ versus +++ 0.02, &&& versus +++ 0.05. Open in new tab Table 4 Recommended duration of antibiotics based on normalization of PCT values in our study Category Days (mean ± SD) Culture-positive sepsis 9.6 ± 3.1 Culture-negative sepsis 6.4 ± 3.1 Neonates with septic shock 9.6 ± 4.2 Neonates without shock 6.2 ± 2.5 Early-onset sepsis 7.8 ± 3.9 Late-onset sepsis 6.9 ± 3.4 Based on SIRS staging Sepsis 5.8 ± 2.6 Sepsis syndrome 6.1 ± 3.1 Early septic shock 6.3 ± 3.3 Refractory shock with MODS 9.4 ± 3.6 Category Days (mean ± SD) Culture-positive sepsis 9.6 ± 3.1 Culture-negative sepsis 6.4 ± 3.1 Neonates with septic shock 9.6 ± 4.2 Neonates without shock 6.2 ± 2.5 Early-onset sepsis 7.8 ± 3.9 Late-onset sepsis 6.9 ± 3.4 Based on SIRS staging Sepsis 5.8 ± 2.6 Sepsis syndrome 6.1 ± 3.1 Early septic shock 6.3 ± 3.3 Refractory shock with MODS 9.4 ± 3.6 Open in new tab Table 4 Recommended duration of antibiotics based on normalization of PCT values in our study Category Days (mean ± SD) Culture-positive sepsis 9.6 ± 3.1 Culture-negative sepsis 6.4 ± 3.1 Neonates with septic shock 9.6 ± 4.2 Neonates without shock 6.2 ± 2.5 Early-onset sepsis 7.8 ± 3.9 Late-onset sepsis 6.9 ± 3.4 Based on SIRS staging Sepsis 5.8 ± 2.6 Sepsis syndrome 6.1 ± 3.1 Early septic shock 6.3 ± 3.3 Refractory shock with MODS 9.4 ± 3.6 Category Days (mean ± SD) Culture-positive sepsis 9.6 ± 3.1 Culture-negative sepsis 6.4 ± 3.1 Neonates with septic shock 9.6 ± 4.2 Neonates without shock 6.2 ± 2.5 Early-onset sepsis 7.8 ± 3.9 Late-onset sepsis 6.9 ± 3.4 Based on SIRS staging Sepsis 5.8 ± 2.6 Sepsis syndrome 6.1 ± 3.1 Early septic shock 6.3 ± 3.3 Refractory shock with MODS 9.4 ± 3.6 Open in new tab There was no recurrence of symptoms or any other morbidity among the survivors up to 4 weeks after discharge. There was no loss to follow-up. DISCUSSION In the present study, the mean duration of antibiotics was 7.2 ± 3.4 days, and time to normalization of PCT levels, resolution of symptoms, duration of antibiotics and duration of stay in hospital were significantly higher in the neonates with shock than in those without shock. Similarly, time to normalization of PCT levels, resolution of symptoms, duration of antibiotics and duration of stay in hospital were significantly higher in the neonates with culture-positive sepsis than in culture-negative sepsis. These parameters were significantly higher in neonates with refractory shock with MODS than in those with sepsis and sepsis syndrome. All surviving neonates with sepsis showed a decrease in PCT levels at the time of clinical resolution after antibiotic therapy, indicating response to therapy [12]. On the basis of the time to normalization of PCT levels in our study, the optimum duration of antibiotics in neonatal sepsis was 9.6 ± 3.1 days in neonates with culture-positive sepsis, 6.4 ± 3.1 days in neonates with culture-negative sepsis, 9.6 ± 4.2 days in neonates with shock and 6.2 ± 2.5 days in neonates without shock. There was no recurrence of symptoms or any other morbidity among the survivors up to 4 weeks after discharge. The duration of antibiotic therapy and hospitalization in neonatal sepsis can be rationalized and optimized by PCT level estimation. Assessment of PCT levels was repeated at clinical resolution of symptoms, and if the levels did not normalize, then the assessment was repeated every 48 h till normalization. This strategy was followed to minimize the frequency of PCT level estimation. Excessive duration of antibiotics increases the potential for bacterial resistance and nosocomial infections, incurs higher hospital costs and may interfere with mother–infant bonding. Prolonged use of antibiotics is also associated with the increased risk of fungal sepsis, necrotizing enterocolitis and death in neonates [13–15]. Sensitivity, specificity, positive predictive value and negative predictive value of CRP level are less compared with those of PCT levels [16–18]. Serial CRP levels have been used to assess clinical response but these have not been assessed for the duration of treatment [6, 7]. The strengths of the study included the presence of a microbiological laboratory functioning throughout the day for timely reporting of blood culture samples and availability of bedside PCT QDx Instacheck Reader for prompt estimation of PCT levels. All neonates were closely monitored to identify those who achieve asymptomaticity and antibiotics were discontinued on the basis of PCT level assessment. All neonates were followed up for 4 weeks for recurrence of symptoms, morbidity and death. Telephonic contact details were obtained and used when required; there was no loss to follow-up. In PRORATA trial on adults with sepsis, stoppage of antibiotics has been recommended once the PCT levels normalize or reduce to ≥80% of the baseline levels [19]. Stocker et al. [1] have shown that PCT-guided decision-making resulted in a shortening of antibiotic therapy by 22.4 y in neonatal sepsis. However, they have not documented the duration of antibiotics and the time of normalization of PCT levels. In the present study, antibiotics were stopped at the time of normalization of PCT levels. There was no morbidity or mortality in the 4-week follow-up. Hence, we recommend that antibiotic therapy can be stopped at the time of normalization of PCT following resolution of symptoms. To conclude, the antibiotic therapy could be optimally stopped at the time of normalization of PCT levels following resolution of symptoms. There was no recurrence of symptoms, morbidity or mortality during the 4-week follow-up. Larger multicentric studies may be conducted to validate these findings. Contributions N B Mathur conceived and designed the study, interpreted the data, finalized the manuscript and is the guarantor. Bijaylaxmi Behera collected the data, drafted and approved the final manuscript. REFERENCES 1 Stocker M , Hop WC , van Rossum AM. Neonatal Procalcitonin Intervention Study (NeoPInS): Effect of Procalcitonin-guided decision making on duration of antibiotic therapy in suspected neonatal early-onset sepsis: a multi-centre randomized superiority and non-inferiority Intervention Study . BMC Pediatr 2010 ; 10 : 89 . 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TI - Blood Procalcitonin Levels and Duration of Antibiotics in Neonatal Sepsis
JF - Journal of Tropical Pediatrics
DO - 10.1093/tropej/fmy053
DA - 2019-08-01
UR - https://www.deepdyve.com/lp/oxford-university-press/blood-procalcitonin-levels-and-duration-of-antibiotics-in-neonatal-JS33smOF0M
SP - 315
VL - 65
IS - 4
DP - DeepDyve
ER -