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ORIGINAL ARTICLE
Year : 2016  |  Volume : 19  |  Issue : 2  |  Page : 89-93

The necessity of full sepsis screen in neonatal sepsis: Experience in a resource-limited setting


1 Department of Medical Microbiology, Jos University Teaching Hospital, PMB 2076, Jos, Nigeria
2 Department of Paediatrics, Jos University Teaching Hospital, PMB 2076, Jos, Nigeria
3 Department of Epidemiology and Community Health, Jos University Teaching Hospital, PMB 2076, Jos, Nigeria

Date of Web Publication12-Jul-2016

Correspondence Address:
Kenneth Ikenna Onyedibe
Department of Medical Microbiology, Jos University Teaching Hospital, PMB 2076, Jos
Nigeria
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DOI: 10.4103/1118-8561.186041

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  Abstract 

Background: Diagnostic tests that differentiate infected from noninfected neonates have the potential to make a significant impact on neonatal care. A full sepsis screen may be necessary to make a diagnosis of neonatal sepsis. Objective: The objective of this study was to evaluate the necessity of routinely collecting blood, urine, and cerebrospinal fluid (CSF) samples from every neonate suspected of sepsis. Materials and Methods: This was a cross-sectional study conducted in a Tertiary Care Hospital in Nigeria. The Integrated Management of Childhood Illnesses (IMCI) criteria for diagnosis of neonatal sepsis were used to select subjects into the study. Blood samples, CSF, and urine samples were collected from 165 neonates and processed by standard microbiologic methods. Results: A total of 68 isolates were recovered from 165 sets of blood culture samples representing 41.2% positive blood culture results. Only 3 (1.8%) organisms were isolated from 165 CSF samples. Five (3%) isolates were recovered from 165 urine samples. The three isolates from CSF were the same with blood isolates from the same neonates. Similarly, four of the five neonates with urine isolates also had blood isolates of the same organism. Conclusion: The findings of this study suggest that a properly collected blood culture sample is the most appropriate sample for recovering the causative organism in neonatal sepsis whereas other samples such as CSF and urine should be collected only when there are specific indications such as an obvious focus of infection in these sites. A full sepsis screen may not be necessary in most cases so as not to put the already sick neonate through unnecessary and sometimes harmful procedures.

Keywords: Full sepsis screen, necessity, resource limited


How to cite this article:
Onyedibe KI, Okolo MO, Toma B, Afolaranmi T. The necessity of full sepsis screen in neonatal sepsis: Experience in a resource-limited setting. Sahel Med J 2016;19:89-93

How to cite this URL:
Onyedibe KI, Okolo MO, Toma B, Afolaranmi T. The necessity of full sepsis screen in neonatal sepsis: Experience in a resource-limited setting. Sahel Med J [serial online] 2016 [cited 2019 Oct 15];19:89-93. Available from: http://www.smjonline.org/text.asp?2016/19/2/89/186041


  Introduction Top


Early diagnosis and treatment of the newborn infant with suspected sepsis is essential to prevent severe and life-threatening complications. In this era of multidrug resistance, it is important to avoid unnecessary use of antibiotics to treat noninfected infants.[1],[2] Thus, diagnostic test(s) that differentiate infected from noninfected neonates has/have the potentials of making a significant impact on neonatal care.[3] Various strategies to reduce morbidity and mortality in newborns with sepsis involve the use of combinations of clinical signs with laboratory investigations for identification and intervention in babies at risk. Unfortunately, clinical signs are nonspecific and often manifest themselves in the absence of a positive culture.[1] Procalcitonin, a precursor of calcitonin, is now being assayed as a specific marker for bacterial infections and rises markedly in sepsis.[4] Polymerase chain reaction (PCR) has proved to be a valuable adjunct for detection of neonatal viral infections. However, the use of PCR to detect bacteremia and fungemia is more challenging and thus is still under investigation.[5] Therefore, the “gold standard” for diagnosing neonatal sepsis remains the blood culture.[6],[7],[8]

In low–middle-income countries such as Nigeria, culture of blood and body fluids by manual methods is the mainstay for the diagnosis of neonatal sepsis. Other laboratory tests such as procalcitonin assay, C-reactive protein assay, automated blood culture systems, PCR techniques, counter immune-electrophoresis, and latex agglutination tests are rarely available and where available, they are either too expensive or not easily accessible. The objective of this study was to determine the necessity of routinely collecting blood, urine, and cerebrospinal fluid (CSF) samples from every neonate suspected of sepsis as part of a full sepsis screen.


  Materials and Methods Top


This study was a cross-sectional study carried out in 2011.

Study area

The study was carried out in the Special Care Baby Unit (SCBU) of the hospital. The SCBU is a 30-bed capacity unit where neonates in need of intensive and special care are managed. The hospital serves as a referral center for most states in the region.

Ethical consideration

Ethical clearance was obtained from the Institutional Research and Ethics Committee. Recruitment of neonates and participation in the study was subject to consent by parents or guardians of the neonates. This consent was obtained from parent or guardian after adequate explanation had been provided before recruitment into the study and collection of samples from the neonates.

Recruitment of participants

Specimens were collected from 165 neonates in the SCBU of the hospital who had a clinical diagnosis or suspicion of neonatal sepsis and whose parents or guardians consented to participate in the study. The WHO young infant study group criteria and the Integrated Management of Childhood Illnesses (IMCI) criteria were used to select subjects for enrollment into the study.[9] A neonate was recruited into the study if the neonate presented with at least one sign in each of the tools after evaluation by a specialist senior registrar in the neonatology unit.

Sample collection

Samples collected include blood (165 sets), CSF (165 samples), and urine (165 samples). Standard aseptic techniques were observed in both collection and processing of samples. Blood for culture was obtained by venipuncture of any two peripheral veins after adequate aseptic preparations. They were inoculated immediately at the site of collection into brain heart infusion broth at a ratio of 1:10 (blood:broth). CSF samples were collected by lumbar puncture (LP) between the 4th and 5th spinal arachnoid space after adequate aseptic preparation. Urine samples were obtained by suprapubic aspiration after ensuring that the neonate had not voided in the preceding 30 min to 1 h. The CSF and urine samples were collected in sterile universal bottles, adequately labeled and transported to the microbiology laboratory immediately.

Laboratory methods

Specimens collected from the neonates were processed in the microbiology laboratory of the hospital by standard methods.[10] The samples collected from each neonate were inoculated on blood agar, chocolate agar (Oxoid, Basingstoke, UK), and MacConkey agar (Fluka medica) plates using a sterile platinum wire loop. MacConkey and blood agar plates were incubated aerobically at a temperature of 35–37°C for 24–48 h, whereas chocolate agar plates were incubated in a candle extinction jar (to provide 5% CO2) to facilitate the growth of fastidious organisms.

Blood cultures were incubated at a temperature of 35–37°C for a period of 1–7 days. The broth cultures were examined macroscopically on a daily basis for gas formation, increased turbidity, or clot formation which may indicate bacterial growth. If any of such macroscopic evidence was seen, an immediate subculture on MacConkey, chocolate, and blood agar plate was carried out and incubated as previously mentioned. Blind subcultures were done from the blood culture broths on days 1, 3, and 7. Inoculated plates were examined the following day for evidence of growth. Isolates were identified by microscopy, culture, and biochemical techniques.[10],[11] Control strains were used for quality control.[10],[11]

Criteria for selection of a true isolate

An isolate was considered to be the true cause of the sepsis in the neonates when it has fulfilled any one of the following criteria:

  • The isolate has been cultured from two blood culture bottles
  • An isolate cultured from one blood culture bottle in the three subcultures in a neonate with frank clinical features of neonatal sepsis and not a known contaminant such as coagulase negative Staphylococci, Pseudomonas aeruginosa, Corynebacterium spp., Fusobacterium spp., Propionibacterium spp., and Bacillus spp
  • An isolate that was cultured from several specimens taken from the same neonate (e.g., blood, CSF, urine) or an isolate from any other site other than blood (e.g. CSF, urine, aspirate, or swab) in a neonate with symptoms and signs
  • All culture bottles or plates with mixed growth (defined as more than two types of bacteria) were discarded and no isolate documented. However, culture bottles and plates with two growths where one of the isolates is a known contaminant (as listed in (ii) above) are processed further with a pure colony obtained by purity plating of the other noncontaminant isolate. Where both isolates were possible contaminants, they were discarded.


Statistical analysis

EPI Info version 3.5.3 developed by Centers for Disease Control and Prevention (CDC) in Atlanta, Georgia (USA) statistical package was used for statistical analysis.


  Results Top


One hundred and sixty-five neonates had their samples collected for bacteriological examination. In this study, 79 (47.9%) and 86 (52.1%) of the neonates were aged ≤3 days and >3 days, respectively. Male neonates were 91 (55.2%) and females 74 (45.8%).

A total of 68 isolates were recovered from 165 sets of blood culture samples of the neonates representing 41.2% positive culture results from blood culture samples. Only 3 (1.8%) organisms were isolated from 165 CSF samples. Five isolates were recovered from 165 urine samples representing 3% of the total urine samples [Figure 1]. There was a statistically significant relationship between the site from which samples were collected and the culture result (P < 0.001).
Figure 1: Distribution of culture results from different specimen types

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Three neonates had both CSF and blood isolates of the same phenotypic organism. Similarly, four of five neonates with urine isolates also had both urine and blood isolates of the same organism phenotypically. The fifth urine isolate which was found only in the urine was P. aeruginosa. A particular neonate had  Escherichia More Details coli from all three samples which were phenotypically identified as the same organism. The distribution of the isolates recovered from different samples is as shown in [Table 1].
Table 1: Frequency of isolates from the different samples collected from the neonates studied

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  Discussion Top


A full sepsis work-up in a neonate suspected of an infection involves the collection of blood sample, CSF sample, urine sample as well as aspirates and swabs from discharging sites if any from the same neonate. Is this necessary for every neonate suspected of an infection? Is a full sepsis work-up cost-effective? Neonatologists are faced everyday with the dilemma of making a diagnosis of neonatal sepsis in a neonate who does not localize the focus of an infection and usually presenting with subtle clinical signs and symptoms. These considerations are even more apt in low–middle-income countries like ours where resources are limited.

In this study, only 3 (1.8%) isolates were cultured from the CSF, these isolates were also recovered from the blood of the same neonates. Five organisms were isolated from the urine. Of the five, only P. aeruginosa was not found in the blood of the same neonate. These findings bring to fore the controversy on whether to put a neonate through the rigors of a complete sepsis work-up by taking samples such as urine and CSF when organisms in these sites are most often also present in the blood of such neonates. In Ilorin, Nigeria, the necessity of an LP in already sick neonates was evaluated by Ajayi and Mokuolu [12], and they concluded that the trauma of an LP could worsen the outcome of such neonates, especially if presentation is in the first 72 h of life, at an age when the newborn is still very fragile.[12] These findings were also in agreement with other studies in Europe and America where an LP is only considered when a blood culture is negative and the neonate have obvious signs of meningitis such as a bulging anterior fontanel with elevated temperatures.[13],[14] The findings of this study support the assertion that an LP should not rank high on the list of laboratory investigations routinely required in neonatal sepsis. Moreover, LP and suprapubic tap are invasive procedures which are not only traumatizing to the neonate but also could be a source of nosocomial infection to the already sick neonate.

In addition, the direct cost of collecting and processing a set of blood culture sample, urine sample, and a CSF sample by manual methods in our institution is about 4000 Nigerian Naira (20 dollars). This includes the cost of disinfectant and consumables used in collecting the samples. This cost will be at least double if it were in a private hospital. Collecting and processing only a set of blood culture sample by manual methods will cost about 2000 Nigerian Naira (10 dollars) per neonate and will save the patient another 10 dollars in direct costs. This also saves the clinicians and the laboratory personnel the time, energy, and logistics required in collecting and processing CSF and urine samples when these samples may not be necessary. The automated blood culture systems where available usually cost up to 10,000 Nigerian Naira (50 dollars) for each neonate sampled and if this is added to urine and CSF cultures, the cost becomes unaffordable and highly prohibitive to the average individual in our setting. The untoward impact of socioeconomic factors on neonatal sepsis in Nigeria has been evaluated previously.[15]

However, technical difficulties associated with phlebotomy in small, sick preterm neonates often limit the volume of blood obtained and thus decrease the sensitivity of blood cultures in diagnosing sepsis.[7],[8] Important procedures to improve the sensitivity and specificity of blood cultures include proper skin disinfection before collection, culturing early in the septic episode, taking an appropriate volume of blood per culture, and if collecting through an existing intravenous device, ensuring a peripheral culture is also collected and where practical, more than one bottle per episode.[11] Unfortunately, this is not always feasible in a very tiny infant.[7],[8] Stringent efforts were made to meet these requirements in this study for optimum recovery of organisms from the blood culture.

Moreover, diagnostic methods such as procalcitonin assay, latex agglutination, counter immune-electrophoresis, and PCR—if available—are still much more expensive than the use of blood cultures. A major concern about bacterial PCR is possible contamination due to the widespread presence of bacterial DNA in the environment, which may be a major stumbling block to clinical applications.[2],[5] Procalcitonin assays and C-reactive proteins are nonspecific and only serve as a pointer to bacterial infection. Counter immune-electrophoresis and latex agglutination tests detect antigen in body fluids (e.g. CSF, concentrated urine); they can be used when antibiotic pretreatment renders culture results unreliable. They may also detect capsular polysaccharide antigen of Group B Streptococci, E. coli K1,  Neisseria More Details meningitidis type B, Streptococcus pneumoniae, and Haemophilus influenzae type B.[8] Because latex agglutination and counter immune-electrophoresis can only detect a few specific organisms, it is still more reasonable to use blood cultures from where the causative agent could be isolated and antibiotic susceptibility testing easily performed.

From the standpoint of laboratory practice, when examining some of the data published on the laboratory aids for diagnosis of neonatal sepsis, it is obvious that differences in laboratory techniques have also been partially responsible for the conflicting opinions about the necessity of a given test.[4],[5],[7],[8] The techniques employed in this study were all standard sample collection and microbiologic techniques.[10],[11] The identification of any isolate as a true isolate was only after appropriate scrutiny, medical evidence, and pathogenicity of the isolate as documented in the aforementioned criteria for isolates selected as the true cause of sepsis in the neonates. We hope that the automated culture systems are made available in our centers to improve yield and turnaround time for blood culture tests.

Finally, the justification for full sepsis screen has always been that neonates localize infection poorly. Neonatologists will require convincing evidence that there are more reliable ways of early detection and prevention of the grave complications of sepsis in a neonate such as irreversible neurological damage before they may be able to discard such a longstanding and strong basis of practice. It was never intended that this study will change such practice but could serve as a catalyst for more studies on the necessity of a full sepsis screen and the continued search for more reliable methods of detection of sepsis in the neonate.


  Conclusion Top


The findings of this study suggest that a properly collected blood culture sample is the most appropriate sample for recovering the causative organism in neonatal sepsis, whereas other samples such as aspirates, swabs, CSF, and urine should be taken only when there are specific indications such as an obvious focus of infection in these sites. A full sepsis screen and even the more sophisticated molecular techniques may not be necessary in most cases so as not to put the already sick neonate through unnecessary and sometimes harmful procedures.

Acknowledgment

The authors would like to acknowledge and thank Professors Fidelia Bode-Thomas, Daniel Z. Egah, and Edmund B Banwat for their supervision, criticism, and contributions to the success of this work. We would also like to acknowledge the input of neonatologists and all the staff of the SCBU, the EPU, and the medical microbiology departments of the Jos University Teaching Hospital.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
  References Top

1.
Musoke RN, Revathi G. Emergence of multidrug-resistant gram-negative organisms in a neonatal unit and the therapeutic implications. J Trop Pediatr 2000;46:86-91.  Back to cited text no. 1
    
2.
Onyedibe KI, Bode-Thomas F, Nwadike V, Afolaranmi T, Okolo MO, Uket OO, et al . High rates of bacteria isolates of neonatal sepsis with multidrug resistance patterns in Jos, Nigeria. Ann Pediatr Child Health 2015;3:1052.  Back to cited text no. 2
    
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Ogunlesi TA, Ogunfowora OB, Osinupebi O, Olanrewaju DM. Changing trends in newborn sepsis in Sagamu, Nigeria: Bacterial aetiology, risk factors and antibiotic susceptibility. J Paediatr Child Health 2011;47:5-11.  Back to cited text no. 3
    
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Infection in the Neonate, Merck Manual Online. Available from: . [Last accessed on 2015 Feb 05].  Back to cited text no. 4
    
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McCabe KM, Khan G, Zhang YH, Mason EO, McCabe ER. Amplification of bacterial DNA using highly conserved sequences: Automated analysis and potential for molecular triage of sepsis. Pediatrics 1995;95:165-9.  Back to cited text no. 5
    
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Kellogg JA, Ferrentino FL, Goodstein MH, Liss J, Shapiro SL, Bankert DA. Frequency of low level bacteremia in infants from birth to two months of age. Pediatr Infect Dis J 1997;16:381-5.  Back to cited text no. 6
    
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Neal PR, Kleiman MB, Reynolds JK, Allen SD, Lemons JA, Yu PL. Volume of blood submitted for culture from neonates. J Clin Microbiol 1986;24:353-6.  Back to cited text no. 7
    
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Kaufman D, Fairchild KD. Clinical microbiology of bacterial and fungal sepsis in very-low-birth-weight infants. Clin Microbiol Rev 2004;17:638-80.  Back to cited text no. 8
    
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Clinical prediction of serious bacterial infections in young infants in developing countries. WHO Young Infants Study Group. Pediatr Infect Dis J 1999;18:23-31.  Back to cited text no. 9
    
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Washington CW, Elmer WK, Koneman R, Stephen DA, Williams M. Koneman's Colour Atlas and Textbook of Diagnostic Microbiology. 6th ed. Baltimore: Lippincott Williams and Wilkins; 2006. p. 431-52.  Back to cited text no. 10
    
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World Health Organization (WHO). Manual for the Laboratory Identification and Antimicrobial Susceptibility Testing of Bacterial Pathogens of Public Health Importance in the Developing World. WHO Report. Geneva: World Health Organization; 2003.  Back to cited text no. 11
    
12.
Ajayi OA, Mokuolu OA. Evaluation of neonates with risk for infection/suspected sepsis: Is routine lumbar puncture necessary in the first 72 hours of life? Trop Med Int Health 1997;2:284-8.  Back to cited text no. 12
    
13.
Weisman LE, Merenstein GB, Steenbarger JR. The effect of lumbar puncture position in sick neonates. Am J Dis Child 1983;137:1077-9.  Back to cited text no. 13
    
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Eldadah M, Frenkel LD, Hiatt IM, Hegyi T. Evaluation of routine lumbar punctures in newborn infants with respiratory distress syndrome. Pediatr Infect Dis J 1987;6:243-6.  Back to cited text no. 14
    
15.
Onyedibe KI, Utoh-Nedosa AU, Okolo MO, Ita OI, Udoh UA, Nedosa IV, et al . Impact of socioeconomic factors on neonatal sepsis in Jos, Nigeria. Jos J Med 2012;6:54-8.  Back to cited text no. 15
    


    Figures

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    Tables

  [Table 1]


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