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ORIGINAL ARTICLE
Year : 2016  |  Volume : 5  |  Issue : 4  |  Page : 254-258

Drug-resistant organism in early-onset and late-onset neonatal sepsis at tertiary care hospital


Department of Paediatrics, Bangabandhu Sheikh Mujib Medical University, Dhaka 1000, Bangladesh

Date of Web Publication16-Nov-2016

Correspondence Address:
Dr. Suraiya Begum
Department of Paediatrics, Bangabandhu Sheikh Mujib Medical University, Dhaka 1000
Bangladesh
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/2249-4847.194171

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  Abstract 

Context: Neonatal sepsis is one of the common reasons for admission to neonatal units in developing countries. Resistance to antibiotics is increasing in neonatal sepsis. Aims: To evaluate the antibiotic resistant pattern of pathogens associated with early-onset and late-onset neonatal sepsis. Settings and Design: This cross-sectional study was done at special care baby unit of a tertiary care hospital from January 2008 to June 2009. Subjects and Methods: All neonates with risk factors or clinical features of sepsis were enrolled and samples for blood cultures were taken. Neonates whose blood culture yielded growth of bacteria were included in this study. Standard data collection form was used to collect all demographic data, pathogen, and resistant to antibiotics. Statistical Analysis Used: Chi-square test and Fisher's exact test were used for compare the variables. The value P< 0.05 was considered statistically significant. Statistical analysis was done using EpiInfo 7. Results: Sixty-five blood culture positive neonates were included in this study. Early-onset neonatal sepsis and late-onset neonatal sepsis were 35.4% and 54.6%, respectively, and 98.5% sepsis was caused by Gram-negative organism. Common organisms isolated were Klebsiella and Enterobacter. Organisms isolated were resistant to first- and second-line antibiotics and quinolone derivatives. In about 15% cases, bacteria showed resistance to third line of antibiotics used in neonatal sepsis. Conclusion: Gram-negative bacteria and in particular Klebsiella and Enterobacter species are the leading causes of early-onset and late-onset neonatal sepsis. All organisms were resistant to ampicillin, gentamicin, and third generation cephalosporin but resistant to imipenem and meropenem were low.

Keywords: Drug-resistant neonatal sepsis, early-onset neonatal sepsis, late-onset neonatal sepsis


How to cite this article:
Begum S, Fatema K. Drug-resistant organism in early-onset and late-onset neonatal sepsis at tertiary care hospital. J Clin Neonatol 2016;5:254-8

How to cite this URL:
Begum S, Fatema K. Drug-resistant organism in early-onset and late-onset neonatal sepsis at tertiary care hospital. J Clin Neonatol [serial online] 2016 [cited 2019 May 21];5:254-8. Available from: http://www.jcnonweb.com/text.asp?2016/5/4/254/194171


  Introduction Top


Neonatal sepsis is one of the common reasons for admission to neonatal units in developing countries.[1] It is also a major cause of morbidity and mortality in both developed and developing countries.[2] It is estimated that 20% of neonates develop sepsis and approximately 1% death due to sepsis.[3] The spectrum of organisms that cause neonatal sepsis changes over time and varies from region to region. It can even vary from hospital to hospital. Group B Streptococcus and coagulase negative staphylococci are the major pathogens in the early-onset neonatal sepsis (EOS) and late-onset neonatal sepsis (LOS) in the Western countries.[4] Staphylococcus aureus and Gram-negative organism with multidrug-resistant bacteria are becoming increasingly common in South Asia.[5] Knowledge of the pathogens causing such infections is essential for appropriate management strategies. In most of the developing countries, Gram-negative organisms remain the major cause of neonatal sepsis, particularly early-onset neonatal sepsis.[6] These organisms have developed drug resistance over the last two decades due to the indiscriminate and inappropriate use of antibiotics.[7] The rapid emergence of drug resistant neonatal sepsis in developing countries is a new potential threat to the survival of newborn babies, who are often already in poor condition. Continued local surveillance is needed to monitoring emerging bacterial resistance, avoiding the irrational use of antibiotic, and minimizing the occurrence of sepsis by resistant organism by hand washing, control of visitors, and proper cleaning of instruments using in neonatal Intensive Care Unit is mandatory.


  Subjects and Methods Top


This was a cross-sectional study carried out at special care baby unit of a tertiary care hospital from January 2008 to June 2009. Ethical approval has been taken before beginning the study. All neonates with clinical features of sepsis or with risk factors for sepsis were enrolled, and samples for blood cultures were taken before administration of antibiotics in all cases and also when not responding to antibiotics according to protocol of neonatal Intensive Care Unit. Neonates whose blood culture yielded growth of bacteria were included in this study. For the study purpose, we categorized sepsis in two groups; early-onset neonatal sepsis (EOS) where onset of sepsis within 3 days of delivery and late-onset neonatal sepsis (LOS) where onset of sepsis at >3 days of life. Data including sex, age, clinical features consistent with sepsis, results of cultures, antibiotic resistance, and clinical outcome of the patients were entered into a standard data collection sheet. Blood culture samples were aseptically collected by the doctors into the blood culture broth and were sent to the laboratory where they were handled according to the manufacturer's specifications. The antibiotic sensitivity tests were carried out by disk diffusion method. First-line antibiotics were ampicillin and aminoglycosides, second-line antibiotics were third generation cephalosporin, and third line antibiotics were imipenem and meropenem used in this study.

Statistical methods

Chi-square test and Fisher's exact test were used for compare the variables. The value P < 0.05 was considered statistically significant. Statistical analysis was done using EpiInfo 7.


  Results Top


Sixty-five blood culture positive neonates were included in this study, in which 61.54% were preterm, 38.46% were term, and 70% were low birth weight (LBW), very LBW (VLBW), and extremely LBW (ELBW). Majorities were delivered by cesarean section (72.31%), inborn and outborn were equal in number, male and female ratio was 1:1.1, and EOS and LOS were 35.4% and 54.6%, respectively. Demographic characteristics between two groups were not statistically significant [Table 1]. EOS almost equal in both term and preterm and LOS was more in preterm than term (69.05% vs. 30.95%) but statistically not significant.
Table 1: Demographic characteristics of neonate (n=65)

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In this study, 98.5% sepsis was caused by Gram-negative organism, in which 52.3% sepsis was caused by Klebsiella. Second most common organism was Enterobacter (21.5%). Other organisms were Acinetobacter (10.8%), Pseudomonas (7.7%), Serratia (3.1%), and Citrobacter (3.1%). Gram-positive organism (Staphylococcus) was found in only one neonate. Sepsis with Klebsiella, Pseudomonas, Serratia, and Citrobacter was found equally in EOS and LOS. Acinetobacter were more common organism in EOS and Enterobacter was more in LOS [Table 2].
Table 2: Organism isolated from blood culture (n=65)

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The organisms were found resistant to ampicillin, gentamicin, ceftazidime, chloramphenicol, co-trimoxazole, and netilmicin in 93.85%, 89.23%, 84.62%, 93.85%, 89.23%, and 83.08% cases, respectively. In this study, resistance to amikacin and ciprofloxacin was found in 74% and 77% cases. Resistance of bacteria to imipenem and meropenem was low (16.92% and 15.38% respectively) [Table 3]. Klebsiella was 100% resistant to ampicillin and gentamicin.Klebsiella and Enterobacter were highly resistant to third generation cephalosporin, but resistance of Pseudomonas to ceftazidime (20%) was low. In this study, all the organisms showed less resistance to imipenem and meropenem. Some organisms showed moderate resistance to gentamicin, amikacin, and netilmicin. Serratia, Citrobacter, and Staphylococcus were highly resistant organism observed in this study [Table 4].
Table 3: Distribution of resistant pattern of antibiotics in early-onset neonatal sepsis and late-onset neonatal sepsis

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Table 4: Distribution of antibiotic resistant pattern of organism isolated by blood culture

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Resistant pattern was similar in both EOS and LOS. Overall mortality due to sepsis was found in 7 (10.8%) cases in this study and more in LOS (14.3%) than EOS (4.3%).


  Discussion Top


Neonatal sepsis is a life-threatening emergency, and any delay in treatment may result in death. The spectrum of organisms causing neonatal sepsis in our study is similar to other neonatal units in developing countries.[8] We found that LOS was more common than EOS (64.4% vs. 35.6%), consistent with few studies, but contrast with some studies where EOS was more common than LOS.[9],[10],[11] In our study, 70% LOS was observed in preterm babies and 80% LOS was in LBW, VLBW, and ELBW, but not statistacally significant. Preterm delivery, LBW, and VLBW were associated with neonatal sepsis by Shah and Desai also.[11] Sepsis was more in these groups of neonates as they are more vulnerable to infection due to immaturity of immune system, prolonged hospital stay, inadequate hand washing, and use of equipment such as continuous positive airway pressure, ventilator, and intravenously access.

Gram-negative organisms were responsible for sepsis in most cases as our study. Klebsiella, Enterobacter, Acinetobacter, and Pseudomonas were common organisms isolated in our study, similar to Rahman et al. and Litzow et al.[12],[13] In our study, Klebsiella was responsible for 52.3% neonatal sepsis which was the most common organism, Litzow et al. from the Philippines, Bhutta and Yusuf from India, Kayange from Tanzania, and Walliullah from Bangladesh reported that Klebsiella was the most common causative organism of neonatal sepsis.[13],[14],[15],[16] Orrett and Shurland, Greenberg et al. and Joshi et al. observed that Klebsiella was the second most common organism in their observation.[17],[18],[19]Enterobacter (21.5%) was the second most common organism in our study and also by Kayange et al. (7.5%) and Ghanshyam et al. (7.5%).[13],[15],[18],[20]Acinetobacter was responsible for neonatal sepsis in 10.8% cases in this study, similar to a study by De et al. He found the incidence of neonatal septicemia by Acinetobacter species was 9.18%.[21]

Our study shows a very high degree of resistance to first- and second-line antibiotics used in neonatal sepsis and also to quinolone derivatives. Resistant pattern was similar in both EOS and LOS. Third line antibiotics used in neonatal sepsis showed resistant in 15% cases in our study. Anwer et al. and Rahman et al. also found a high degree of resistance to ampicillin and gentamicin moderate resistance to cephalosporins and low resistance to quinolone derivative.[1],[22] They observed 80% resistance to ampicillin, 11%–13% resistance to cefotaxime, and 0%–10% resistance to amikacin. Bhutta et al. also reported a high degree of resistance to ampicillin and gentamicin among Gram-negative organisms.[23] Resistant pattern of antibiotics used in neonatal sepsis varies in different countries, but first line antibiotics are highly resistant. Increasing resistance to commonly used first- and second-line antibiotics over the last several years was noted. Routine bacterial surveillance and study of their resistance patterns must be an essential component of neonatal care unit. Infection with resistant organisms has been associated with treatment failure, higher morbidity and mortality, and increased costs. This has necessitated the development, implementation, and evaluation of policies on the use of antibiotics Klebsiella was 100% resistant to ampicillin, gentamicin, and ceftazidime, highly resistant to other aminoglycosides, moderate resistant to fluoroquinolone, and low resistant to imipenem and meropenem. This observation was similar to a study done by Roy et al. Resistant pattern of Enterobacter was almost similar to Klebsiella.[24] Our study shows high resistance to first line and second line antibiotics and emerging resistance to third line antibiotics used in neonatal sepsis. The rate of resistance to most antibiotics was alarming. However, drug-resistant pathogens have already become an important cause of neonatal sepsis, interruption of the transmission of these pathogens through improved infection control practices are necessity.

Acinetobacter was 100% resistant to ampicillin and moderate resistant to aminoglycosides, third generation cephalosporin, fluoroquinolone, imipenem, and meropenem in our study. De et al. found Acinetobacter was more resistant than our study.[21] Resistant pattern of Acinetobacter was different in another study. They found highly resistant to most antibiotics used in neonatal sepsis except imipenem and meropenem.[25]Pseudomonas was 100% resistant to netilmicin, 40% to ampicillin, 60% to other aminoglycosides, and 75% to cefotaxime and ciprofloxacin. Resistant of Pseudomonas was low to ceftazidime, imipenem, and meropenem (20% each) in our study. Pseudomonas was 100% resistant to ampicillin observed by Moniri et al. and Mustafa and Ahmed, but in our study, it was 40%.[26],[27] Resistant of Pseudomonas to amikacin and gentamicin was lower by Moniri et al. than our study (60% vs. 25%).[26] Mutlu et al. found 7% resistant to imipenem and meropenem, but in our study, it was 20% each.[28]Serratia, Citrobacter, and Staphylococcus were highly resistant to cephalosporin group of drugs but sensitive to imipenem and meropenem. Another study showed variable result than our study.[29] Koksal from India reported that neonatal sepsis was caused by Gram-negative organism resistant to ampicillin, amoxicillin, ticarcillin, cefazolin, cefotaxime, ceftazidime, ceftriaxone, and aminoglycoside. They treated these babies with meropenem and achieved 94.3% response.[30] Ampicillin and gentamicin combination as first-line treatment of neonatal sepsis may no longer be effective as empirical therapy. The study population was small, so further study is needed for the use of appropriate first-line antibiotic in neonatal sepsis.


  Conclusion Top


Gram-negative bacteria and in particular Klebsiella and Enterobacter species are the leading causes of early-onset and late-onset neonatal sepsis. All organisms showed high resistance to ampicillin, gentamicin, and third generation of cephalosporin and resistant of imipenem and meropenem was low. Antibiotic resistance is alarming in neonatal sepsis. Routine bacterial surveillance and study of their resistance patterns must be an essential component of neonatal care.

Acknowledgment

We would like to thank parents, doctors, and nurses of special care baby unit. We also grateful to doctors and technicians of microbiological laboratory, for their contribution.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
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