Objective: To identify the validity of surveillance cultures in predicting causative organism(s) of late onset neonatal sepsis. Results: Prospective analytical study was conducted from January to April 2011 at the Neonatal Intensive Care Unit, Teaching Hospital, Karapitiya, Galle, Sri Lanka. Fifty neonates were screened on admission and weekly thereafter for colonization with potential pathogens. On suspicion of infection, relevant samples were cultured and tested for antibiotic sensitivity. There were 55 episodes of clinically suspected infections including 33 nosocomial infections. One-third (17/55) of all clinically suspected infections were culture positive. Out of 55, only 33 episodes were clinically suspected nosocomial infections. Clinically suspected nosocomial infection rate was 50/1000 patient-days. Culture proven nosocomial infection rate was 13.61/1000 patient-days. Coliforms were the commonest clinical isolate (76%) and 2/3 of them produced extended spectrum β lactamase. More than 80% of the isolates causing late onset sepsis were sensitive to carbapenems and aminoglycosides. Sensitivity, specificity, positive predictive value and negative predictive value of surveillance cultures were 77.8, 37.5, 31.8 and 81.8%, respectively. Surveillance samples can be used to predict pathogens of late-onset sepsis. Broad-spectrum antibiotics (carbapenems, aminoglycosides) are rec- ommended as empirical therapy for late-onset neonatal sepsis. Keywords: Empirical antibiotics, Neonatal infections, Surveillance swabs Neonatal sepsis causes approximately 1.6 million neo Introduction - Neonatal infections continue to be a major cause of natal deaths annually in developing countries . A morbidity and mortality in newborns throughout the Malaysian study reports rates of neonatal sepsis of 5–10% world [1, 2]. The increasing populations of very low birth with case fatality rates 23–52% . Klein et al. have weight (VLBW) premature infants, who now survive due shown that neurological sequelae as a complication in to improved neonatal care, represent the group at highest 20–30% of survivors of neonatal bacteraemia and 40% or risk for infections. Neonatal infections are divided into more of those with meningitis . two main categories, early onset sepsis (EOS); infections NICU at the Teaching Hospital Karapitiya (THK) is occurring during the first 48 h of life and late onset sepsis among the few NICUs with level 3 facilities in the coun- (LOS); infections occurring thereafter. try. It receives neonates with various surgical and medical problems from other institutions in Southern province of Sri Lanka. Hospital data from the Microbiology and *Correspondence: firstname.lastname@example.org Department of Microbiology, Faculty of Medicine, University of Ruhuna, Infection Control Unit of THK showed that during 2009 Inland Hill Road, PO Box 70, Galle, Sri Lanka and 2010 there had been three clusters of neonatal sepsis Full list of author information is available at the end of the article © The Author(s) 2018. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creat iveco mmons .org/licen ses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creat iveco mmons .org/ publi cdoma in/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Weerasinghe et al. BMC Res Notes (2018) 11:340 Page 2 of 5 caused by extended spectrum beta lactamase (ESBL) pro- by Sri Lanka College of Microbiologists in Laboratory ducing coliforms in this NICU with increased mortality. Manual in Microbiology, which is again based on CDC Delayed first effective antibiotic dose due to inappro - guidelines . Organisms were identified using colony priate empirical antibiotic therapy is a main reason for morphology, microscopic features and routine bio-chem- delayed recovery and high mortality [6, 7]. It is noted ical tests like catalase test, coagulase test and oxidase test. that prospective studies on neonatal infections and sur- API 20E and streptococcal grouping test kits were used veillance cultures have not been conducted in this unit to identify blood culture isolates of Enterobacteriaceae previously making it is a timely necessity to identify the and streptococci. Antibiotic sensitivity testing (ABST) causative pathogens and their current susceptibility pat- and interpretation of results were done according to pro- terns. The main objective of this study was to examine tocols given by Clinical Laboratory Standards Institute the validity of surveillance cultures in predicting causa- . ABSTs were performed by disc diffusion method or tive organism(s) of late onset neonatal sepsis. E strip method, on all significant isolates. The culture and ABST results of surveillance and clinical samples were Main text documented. Most effective empirical antibiotic therapy Materials and methods was decided using the ABST patterns of clinical isolates. A hospital based prospective study was conducted with a Descriptive analysis of the sample subjects in relation to cohort of fifty neonates admitted to the NICU at the THK age, gestational age at birth, birth weight, EOS and LOS th from 1st January 2011 to 30 April 2011. Babies whose were conducted. Rates of EOS and LOS were calculated age was less than 28 days on admission to the NICU were per 1000 admissions. Rate of nosocomial infections were recruited for the study and they were followed until 48 h calculated for 1000 patient-days of observation. Antibi- of discharge from the NICU or for 48 h after completing otic resistance rates were calculated as percentages. 28 days of age while in the NICU. When assessing the Sensitivity, specificity, positive predictive value and value of surveillance cultures in predicting pathogens of negative predictive value of surveillance cultures in pre- LOS, only the episodes of infections developed follow- dicting organisms causing subsequent infections were ing 48 h of admission to the NICU, were considered. The calculated. infection episodes present on admission to the unit were excluded from the analysis. However, if they developed Results another episode of infection during the NICU stay those Admission age ranged from 1 to 27 days and male babies occasions were considered for the analysis. Therefore consisted 58% of the sample. Birth weights ranged from only 33 episodes of LOS acquired during the NICU stay 0.7 kg to 3.6 kg with a mean of 2.2 kg. Twenty-six babies among 50 neonates were analyzed to assess the value of were preterm and mean gestational age of the study surveillance cultures. Data regarding patients’ demogra- group was 34 weeks + 4 days. All the neonates admit- phy, risk factors for sepsis, signs and symptoms, investi- ted to this NICU had been transferred from outsta- gation results and antibiotic treatment were recorded. tions in Southern province. These admissions were for A peripheral blood culture, deep ear swab, nasal swab, the management of various problems like prematurity, umbilical swab and a rectal swab were collected for cul- sub optimal birth weight, meconium aspiration, respira- ture, from every neonate on admission to the unit. Dur- tory distress, infections etc. Probable risk factors which ing the stay, babies were screened weekly with a rectal made the study participants more vulnerable for infec- swab and respiratory tract secretion cultures; pharyn- tions included very low birth weight, prematurity, cardiac geal aspirates (PA) and gastric aspirates (GA) from non- anomalies, congenital diaphragmatic hernia, ventriculo- intubated babies and endotracheal (ET) secretions from peritoneal shunt, abdominal surgery, prolonged mechan- intubated babies. Clinical suspicion of sepsis in babies ical ventilation, central lines for more than 48 h and was based on criteria from different studies  and deci - intra-partum problems like meconium aspiration with sion of the clinicians treating patients. Haematological birth asphyxia, obstructed-prolonged labour and prema- and biochemical parameters were also used to support ture rupture of membranes. the diagnosis of sepsis. Appropriate clinical specimens Twelve out of 50 admissions had clinically suspected were collected from babies for culture. Centre for Disease EOS (240 per 1000 admissions) which was present on Control and Prevention (CDC) guidelines were followed admission. LOS was noted in 43 occasions (860 per 1000 in collection and transport of specimens . Prepared admissions) and 33 of this was considered to be acquired guidelines were given to staff of the NICU for proper during 661 NICU patient days. The rest (n = 10) was specimen collection and transport for bacteriological cul- identified on admission. Therefore, clinically suspected tures. Specimens were cultured and organisms were iden- nosocomial infection rate was 50 per 1000 patient days. tified according to standard operating procedures given Culture proven rates for EOS and LOS were 2 and 15 Weerasinghe et al. BMC Res Notes (2018) 11:340 Page 3 of 5 episodes (40 and 300 per 1000 admissions), respectively. in Table 3. Sensitivity, specificity, positive predictive Culture proven nosocomial infection rate was 9 for 661 value and negative predictive value of surveillance swabs patient days (13.61 per 1000 patient days). in predicting the organisms of late onset neonatal sepsis Gram negatives accounts for the majority of infec- were calculated as are 77.8, 37.5, 31.8 and 81.8%, respec- tions (70.5%) and septicaemia with no apparent primary tively. Five out of 7 (71. 4%) occasions where we isolated focus was the commonest cause for positive blood cul- the pathogen of infection beforehand in surveillance cul- ture (Table 1). In more than 90% of the occasions bac- tures were from rectal swabs. teraemia was due to coliforms and, extended spectrum beta lactamase (ESBL) producing Klebsiella pneumoniae Discussion pneumoniae was the commonest pathogen in blood cul- Early prediction of pathogens of nosocomial sepsis is tures (72.7%) (Table 2) Almost all (90%) of the coliforms proven to be of value in starting effective first dose anti - were resistant to beta lactam – beta lactamase inhibitors biotic therapy without delay and improving patient and third generation cephalosporin. Among aminoglyco- outcome [6, 7]. Nosocomial pathogens are known to sides, gentamicin was the least sensitive while amikacin be acquired in different ways; cross infection from showed 7.7% resistance. On admission, the commonest other infected patients, colonized healthcare workers, surface colonizer was coagulase negative Staphylococcus (CoNS) (50%), followed by coliforms (40%) and methicil- lin resistant Staphylococcus aureus (MRSA) (10%). From Table 3 Relationship between clinical cultures rectal swabs, coliforms were isolated as the commonest and surveillance cultures in LOS acquired during NICU stay (48.5%). (nosocomial infections) Relationship between clinical and surveillance cultures LOS episodes acquired Surveillance Surveillance in LOS episodes acquired during the NICU stay is shown during NICU stay culture positive culture negative Table 1 Distribution of organisms in this study Clinical culture positive (9) 7 2 as per infections Clinical culture negative (24) 15 9 Total (33) 22 11 Infection type Number Organism (%) of cases Clinical cultures—cultures done on suspicion of infection Surveillance cultures—cultures done on admission from anterior nares, Septicemia 6 Coliform (100%) umbilical swabs, respiratory secretions and rectal swabs and weekly during the Shunt infection 1 Coliform (100%) NICU stay from respiratory secretions and rectal swabs Nectrotizing enterocolitis 2 Coliform (100%) Surveillance culture positive—with regard to culture positive infection episodes, if we have isolated the same organism in a surveillance sample beforehand or Ventilator associated pneu- 2 Coliform (100%) with regard to culture negative infection episodes, if we have isolated a possible monia pathogenic organism as a colonizer in any surveillance sample Meningitis 3 Coliform (66.6%) Streptococcus Surveillance culture negative—with regard to culture positive infection pneumoniae (33.3%) episodes, if we have not isolated the same organism or isolated a different Congenital pneumonia 1 Enterococcus (100%) organism in any of the surveillance samples beforehand. With regard to culture negative infection episodes, if we have not isolated any possible pathogenic Nosocomial pneumonia 2 Acinetobacter (50%) CoNS organism as a colonizer they were also considered as screening negative (50%) occasions Table 2 Distribution of pathogens in different types of clinical samples Type of specimen Pathogen Number of episodes Total On admission During NICU Blood ESBL producing coliforms (Klebsiella pneumo- 8 3 5 niae pneumoniae) Non-ESBL coliforms (Proteus spp.) 2 2 – Strep. pneumoniae 1 1 – Respiratory secretions (ET, PA, GA) ESBL producing coliform spp. 2 – 2 Enterococcus spp. 1 1 – Coag. Neg. Staphylococcus 1 1 – Acinetobacter spp. 1 1 – CSF (from EVD shunt) ESBL producing coliforms 1 – 1 ESBL Extended spectrum beta lactamase; ET endo-tracheal; PA pharyngeal aspirate; GA gastric aspirate; CSF cerebrospinal fluid; EVD external ventricular drain Weerasinghe et al. BMC Res Notes (2018) 11:340 Page 4 of 5 contaminated equipment and the endogenous flora of the the predominating pathogens in the pre-antibiotic era, patient him/herself [11–13]. Therefore surveillance cul - while in 1940s and 1950s Gram negative organisms, par- tures were used in this study to identify potential patho- ticularly Escherichia coli has become the most common gens in endogenous flora. pathogen [20, 21]. The value of routine surveillance of surface colonizers Considering the ABST patterns of coliforms in culture in neonates is a controversial issue. According to Jolley proven LOS we recommend carbapenems and aminogly- some studies show surface swabs are inefficient and not cosides as the most effective empirical antibiotic therapy. cost effective for guiding empirical therapy of neonatal This is emphasized by the fact that rectal swabs being sepsis while some have shown value with surveillance the most useful surveillance cultures, which isolated ET cultures in perinatal pneumonia . In 77.8% of the ESBL producing coliforms. Different findings have been nosocomial infection episodes, we can predict the causa- obtained from another study recommending combined tive pathogen using the isolates in surveillance samples, vancomycin and amikacin for empirical therapy . which is much higher than the findings of De Jong, where they could predict the potential pathogen in 41% of the infections by surveillance cultures . Most useful sur- Conclusions veillance culture type was rectal swabs, which yielded the Overall, surveillance cultures have a good sensitivity in same organism as in clinical sample in 71.4% occasions. prediction of pathogens of LOS in neonates. Nasal swabs, This is a useful finding, especially in order to prevent use respiratory secretions and umbilical swabs are of limited of inappropriate antibiotics in empirical therapy. On the value as screening samples. However, routine surveil- other hand, collecting surface swabs is non-invasive and lance with rectal swabs is useful in neonates to predict easy to perform on neonates. the likely pathogens of LOS and guiding the empirical Since high prevalence of antimicrobial resistance in the antibiotic therapy of nosocomial LOS. unit can affect the effective empirical antibiotic therapy, we analyzed all the clinical cultures and found that there is a high discrepancy between clinically suspected infec- Limitations tion rate and the culture proven rate. This could be due Due to limited time factor available for this study and to several reasons like low threshold for clinical suspicion considering the number of admissions to this unit we had of sepsis in neonates, commencing antibiotic therapy to limit the sample size to 50. Anaerobic cultures could prior to collection of cultures and practical difficulties not be done due to limited resources. in repeated and adequate sample collection for cultures from neonates. Abbreviations Overall nosocomial infection rate of culture proven ABST: antibiotic sensitivity test; CoNS: coagulase negative Staphylococcus; EOS: sepsis, 13.61 episodes per 1000 patient days seems to be early onset sepsis; ESBL: extended spectrum beta lactamase; ET: endotracheal; EVD: external ventricular drain; GA: gastric aspirate; LOS: late onset sepsis; higher than in studies from developed countries. Neo- MRSA: methicillin resistant Staphylococcus aureus; NEC: necrotizing entero-coli- natal nosocomial infection rates across the Australian tis; NICU: Neonatal Intensive Care Unit; PA: pharyngeal aspirate; THK: Teaching and New Zealand network 2009, had found an overall Hospital Karapitiya; VAP: ventilator associated pneumonia. rate of 5.02 episodes of infections per 1000 patient days Authors’ contributions for infants of less than 1000 g birth weight . How- NPW designed and wrote the study plan and was involved in data collec- ever, blood stream infection rate of 7.56 per 1000 patient tion, analysis and writing of the manuscript. DV also designed and wrote the study plan and was involved in analyzing and writing of the manuscript. BP days is compatible with the findings in Gastmeier et al. designed the study sample, analyzed data and involved in critical revision. which have recorded a rate of 6.4 per 1000 days in a less HMMH and AdeN contributed intellectually largely in the final revisions of the than 1000 g birth cohort from Berlin. . Gram nega- manuscript. All authors read and approved the final manuscript. tive organisms predominated as pathogens, which is Author details similar to what was reported from neonatal units in other Department of Microbiology, Faculty of Medicine, University of Ruhuna, developing countries [18, 19]. Two clusters of Klebsiella Inland Hill Road, PO Box 70, Galle, Sri Lanka. Department of Microbiology, Teaching Hospital, Karapitiya, PO Box 70, Galle, Sri Lanka. Department pneumoniae pneumoniae bacteraemias occurred dur- of Community Medicine, Faculty of Medicine, University of Ruhuna, PO Box 70, ing this period also has accounted for the high propor- Galle, Sri Lanka. Department of Medicine, Faculty of Medicine, University tion of Gram negatives. Group B streptococcus was not of Ruhuna, PO Box 70, Galle, Sri Lanka. isolated in any of the samples, and can be due to effec - Acknowledgements tive ante-partum screening and intra-partum antibiot- Authors would like to thank the mothers and newborns who participated ics. Studies have shown a shift from Gram positives to in this study, for their contribution to better understanding of the nature of neonatal sepsis and the value of screening swabs. We would like to extend our Gram negatives over the period of time. Gladstone et al. sincere gratitude towards NICU staff and the staff of the Microbiology Labora- have described group A streptococci and S. aureus as tory at THK for their technical assistance. Weerasinghe et al. BMC Res Notes (2018) 11:340 Page 5 of 5 Competing interests 7. Lueangarun S, Leelarasamee A. Impact of inappropriate empiric The authors declare that they have no competing interests. antimicrobial therapy on mortality of septic patients with bacteremia: a retrospective study. Interdiscip Perspect Infect Dis. 2012;2012:765205. Availability of data and materials 8. Collection and transport of clinical specimens—CDC. https ://www.cdc. Most of data generated or analyzed during this study are included in this gov. Accessed 10 July 2017. published article and datasets generated and/or analyzed during the current 9. Handbook of specimen collection and handling in microbiology. https study are available from the corresponding author on reasonable request.://stack s.cdc.gov/view/cdc/7700/cdc_7700_DS1.pdf. Accessed 10 July Consent for publication 10. Performance standards for antimicrobial susceptibility testing. In: Twenty- Not applicable since data were presented only as grouped data, not as first informational supplement. Clinical Laboratory Standard Institute. individual data. 2011;31. 11. Flynn DM, Weinstein RA, Nathan C, Gaston MA, Kabins SA. Patients’ Ethics approval and consent to participate endogenous flora as the source of “nosocomial” Enterobacter in cardiac Ethical approval was obtained from Ethics Review Committee of Faculty of surgery. J Infect Dis. 1987;156:363–8. Medicine, University of Ruhuna, Sri Lanka. Written consent was obtained from 12. Warren JW. Catheter-associated urinary tract infections. Int J Antimicrob each neonate’s mother or the guardian after a clear explanation of the study Agents. 2001;17(4):299–303. objectives and potential health and patient data confidentiality risks. All the 13. Khan HA, Baig FK, Mehboob R. Nosocomial infections: epidemiol- specimen collection was undertaken under aseptic conditions by the experi- ogy, prevention, control and surveillance. Asian Pac J Trop Biomed. enced medical and nursing staff of the NICU. 2017;7(5):478–82. 14. Jolley AE. The value of surveillance cultures on neonatal intensive care Funding units. J Hosp Infect. 1993;25(3):153–9. The study was financially supported by the Ministry of Health, Sri Lanka. 15. De Jong PJ, De Jong MD, Kuijper EdJ, Van der Lelie H. The value of surveillance cultures in neutropenic patients receiving selective intestinal decontamination. Scand J Infect Dis. 2010;25:107–13. Publisher’s Note 16. Gill AW. Analysis of neonatal nosocomial infection rates across Springer Nature remains neutral with regard to jurisdictional claims in pub- the Australian and New Zealand Neonatal Network. J Hosp Infect. lished maps and institutional affiliations. 2009;72(2):155–62. 17. Gastmeier P, Hentschel J, de Veer I, et al. Device associated nosocomial Received: 4 March 2018 Accepted: 21 May 2018 infection surveillance in neonatal intensive care using specific criteria for neonates. J Hosp Infect. 1998;38:51–60. 18. Ashiq B, Jamal M. A study of neonatal aerobic septicaemia. 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