|Year : 2016 | Volume
| Issue : 1 | Page : 67-71
Bacteriological profile and antibiotic sensitivity pattern of neonatal septicaemia in a rural tertiary care hospital in North India
S Thakur1, K Thakur1, A Sood1, S Chaudhary2
1 Department of Microbiology, Dr. RPGMC, Kangra, Tanda, Himachal Pradesh, India
2 Department of Pediatrics, Dr. RPGMC, Kangra, Tanda, Himachal Pradesh, India
|Date of Submission||10-Sep-2014|
|Date of Acceptance||30-Jul-2015|
|Date of Web Publication||15-Jan-2016|
Department of Microbiology, Dr. RPGMC, Kangra, Tanda, Himachal Pradesh
Source of Support: None, Conflict of Interest: None
Background: There is not much published literature on neonatal septicemia available for the Sub-Himalayan region of North India. Hence, we undertook this study to find out the bacteriological profile and antibiotic sensitivity pattern of neonatal septicemia in the neonatal Intensive Care Unit. Material and Methods: Blood cultures were performed for all clinically suspected neonatal septicemia cases for 1-year. Identification of all pathogenic isolates was followed by antibiotic sensitivity testing. Results: We did blood cultures for 450 neonates and 42% were culture positive. Early onset sepsis were 92 (49%) and 96 (51%) were late onset sepsis. Gram-positive isolates were 60% and 40% were Gram-negative. Staphylococcus aureus (40%), coagulase negative Staphylococcus species (16%), non-fermenter group of organisms (NFGOs) (15%), and Klebsiella pneumoniae (10%) were the main isolates. Nasal cannula 101 (54%), birth asphyxia 91 (48%), and prematurity 73 (38%) were the prominent risk factors associated with septicemia. Gram-positive organisms were highly resistant to penicillin (87%) whereas Gram-negative isolates showed high resistance to third generation cephalosporins (53–89%) and aminoglycosides (50–67%). The S. aureus isolates were methicillin-resistant in 41% whereas extended spectrum beta lactamase production was seen in 48% Gram-negative isolates.Conclusion: Our study highlights the recent emergence of Gram-positive organisms as predominant cause of neonatal septicemia in this part of Sub-Himalayan region, along with the review of literature which shows similar results from North India and rest of the world too. Though Gram-negative bacteria still remain the main cause of mortality in neonatal septicemia, we want to dispel the common notion among practitioners that they are the predominant isolates in neonatal septicemia.
Keywords: Blood culture, drug resistance, extended spectrum beta-lactamases, methicillin-resistant Staphylococcus aureus, neonates
|How to cite this article:|
Thakur S, Thakur K, Sood A, Chaudhary S. Bacteriological profile and antibiotic sensitivity pattern of neonatal septicaemia in a rural tertiary care hospital in North India. Indian J Med Microbiol 2016;34:67-71
|How to cite this URL:|
Thakur S, Thakur K, Sood A, Chaudhary S. Bacteriological profile and antibiotic sensitivity pattern of neonatal septicaemia in a rural tertiary care hospital in North India. Indian J Med Microbiol [serial online] 2016 [cited 2019 Jun 26];34:67-71. Available from: http://www.ijmm.org/text.asp?2016/34/1/67/174108
| ~ Introduction|| |
Neonatal septicemia is responsible for approximately 25% of the neonatal deaths in the world  and mostly in developing countries. Increased prevalence of extended spectrum beta-lactamases (ESBLs) and methicillin-resistant Staphylococcus aureus (MRSA) and multiple drug resistant (MDR) strains is a cause of concern in Neonatal Intensive Care Units (NICU) worldwide. Septicemia has been classified as early onset septicemia (EOS) and late-onset septicemia (LOS). The microorganisms most common associated with EOS include Group B Streptococcus (GBS), Escherichia More Details coli, coagulase negative Staphylococcus species (CONS), Haemophilus influenzae and Listeria monocytogene. and LOS is caused by CONS, S. aureus, E. coli, Klebsiella spp., Pseudomonas spp., Enterobacter spp., Candida spp., GBS, Serratia spp., Acinetobacter spp. and anaerobes. The recent trends show an increase in infections due to CONS.
The knowledge of bacteriological profile and its antibiotic sensitivity patterns is of immense help in saving lives of neonates with septicemia.
Although extensive research on neonatal septicemia is available worldwide and in India. However, very few studies have been conducted on neonatal septicemia in the state of Himachal Pradesh and none in this part of the state.
Hence, we undertook a cross-sectional prospective study was to investigate the causative organisms of neonatal septicemia and to assess their antibiotic susceptibility pattern over the period of 1-year in NICU of a tertiary care hospital in the rural area.
| ~ Materials and Methods|| |
The study was conducted after obtaining Institutional Ethics Committee and Institutional Review Board approval.
It was a cross-sectional study carried out in the NICU of a tertiary care medical college and hospital from April 2012 to March 2013. The various neonatal and maternal risk factors were also analysed. The neonatal risk factors studied were low birth weight (LBW), birth asphyxia, meconium staining, congenital anomalies, prematurity, central venous catheterisation >10 days, nasal canula usage, and continuous positive airway pressure use.
The maternal risk factors included socioeconomic status, difficult delivery (caesarean, forceps, vacuum), premature rupture of membranes, prolonged rupture of membranes, maternal fever, recurrent abortions, prenatal care received, urinary tract infection, history of stillbirth, amniocentesis, cervical cerclage operation, and chorioamnionitis.
A total of 450 suspected patients of neonatal septicemia were included in the study. Neonatal septicaemia was suspected if one or more of the following signs and symptoms were present: Convulsions, respiratory rate >60/min, severe chest indrawing, nasal flaring, grunting, bulging fontanelle, pus draining from the ear, redness around umbilicus extending to the skin, temperature ≥37.5°C (99.5°F) or ≤36.4°C (97.52°F), lethargy, unconsciousness, reduced movements, not able to feed, not attaching to the breast, not suckling at all, crepitations in lungs, cyanosis, and reduced digital capillary refill time.
Two millilitres of blood was collected from all neonates aseptically preferably before administration of the antibiotics and inoculated into 20 ml of brain heart infusion broth (Hi-Media, India) on the bedside.
Blood culture bottles were transported immediately to the Microbiology Laboratory and were processed as per standard microbiological techniques and the isolates were identified.
Antibiotic sensitivity testing was performed on Mueller-Hinton agar plates by modified Kirby-Bauer disk diffusion method as per Clinical Laboratory Standard Institute guidelines. E. coli ATCC 25922, S. aureus ATCC 25923, P. aeruginosa ATCC 27853 were used as standard strains. Screening for MRSA was done using a cefoxitin (30 μg) disc. Resistance to ceftazidime (30 μg) disk was used as a screening method for detection of ESBL confirmed by double disk synergy test.
| ~ Results|| |
Of a total of 450 neonates investigated with blood culture, 188 (42%) were found to be positive for neonatal septicemia. Males were 117 (62%) and 71 (38%) females. Mean age at admission was 3.77 ± 5.02 days. Inborn neonates 111 (59%) were more common than outborn 77 (41%). Of 188 neonates, 106 (56%) and 82 (44%) were normal birth weight and LBW neonates, respectively, and 73 (39%) were preterm. Very LBW neonates, that is, weight below 1.5 kg were 19 (11%). EOS and LOS were 92 (49%) and 96 (49%) neonates, respectively. EOS was seen more common in inborn neonates (56%) compared to the outborn (39%).
The common clinical presentations were respiratory distress secondary to birth asphyxia (48%), fever (20%), neonatal jaundice (8.5%), pneumonia (8%), decreased acceptance of feeds and lethargy (7%), and seizures or meningitis (5%). The neonatal risk factors such as birth asphyxia, use of a nasal cannula, and prematurity showed association with culture-proven neonatal septicemia (P < 0.05). None of the maternal risk factors were found to be significantly associated with neonatal septicemia.
Of 188 (42%) positive blood cultures, the Gram-positive bacteria (GPB) and Gram-negative bacteria (GNB) accounted for (60%) and (40%). Respectively, Among Gram-positive organisms, 66% isolates were S. aureus and among Gram-negative organisms, NFGO was the most common organism isolated (40%). Among NFGO, only Acinetobacter spp. (3%) could be identified. Other organisms isolated are summarised in [Table 1].
|Table 1: Gram-positive and Gram--negative pathogens isolated from neonates|
Click here to view
CONS and NFGO were considered as pathogens only if the temperature was >38°C or <36° C, history of initiation of antibiotic therapy or presence of the intravenous catheter.
The resistance to penicillin, amoxicillin and clavulanic acid and azithromycin was 87%, 66% and 48% respectively among GPB and GNB [Figure 1]. Methicillin-resistance was detected in 29 (41%) of S. aureus. There were 30 (40%) MDR isolates among the total of 75 isolates of S. aureus. All the isolates were sensitive to vancomycin.
Gram-negative organisms showed high resistance to the third generation cephalosporins. They also showed high resistance to amoxicillin and clavulanic acid combination (81%), netilmicin (67%) and gentamycin (63%). Resistance to ciprofloxacin and amikacin was observed in (52%) and (50%) respectively [Figure 2]. ESBL production was detected in 24 (48%) of GNB that included Klebsiella pneumoniae 12 (50%), E. coli 6 (25%), NFGO 4 (16%) and Enterobacte r spp. 2 (8%).
High resistance against penicillin and amoxicillin and clavulanic acid was found for both GPB and GNB. The third generation cephalosporin showed weak activity against all tested bacteria. The considerable preponderance of amikacin activity over gentamicin and netilmicin was observed in GNB. Imipenem resistance was observed among 04% GNB. Out of the 45 Enterobacteriaceae isolates in our study 33 (73.3%) were MDR. All the Acinetobacter spp. were also MDR.
There were 22 (12%) mortality which was 17% among female neonates compared to 8.5% among male neonates. Highest mortality of neonates was seen with Klebsiella pneumoniae (27.7%) followed by NFGO (20%) and Enterobacter spp. (20%). The neonatal factors significantly associated with mortality were female sex, LBW, birth asphyxia, and nasal cannula (P < 0.05).
| ~ Discussion|| |
Septicemia remains a significant cause of morbidity and mortality in the newborn. The clinical diagnosis of neonatal septicemia is difficult as it presents with non-specific signs and symptoms. An early diagnosis of neonatal septicemia is important to initiate appropriate and prompt treatment. The correct and timely identification of infectious agents and their antibiotic sensitivity patterns are essential to guide the clinicians regarding both the empirical and definitive treatment.
The bacteriological profile of septicemia keeps changing with the passage of time from region to region and hospital to hospital, in the same city or country. The emergence of resistant bacteria in NICU settings leads to failure in the treatment of neonatal septicemia. To supplement the management of septicemia in neonates, we need to do longitudinal surveillance of the NICUs and formulate periodic guidelines for empirical treatment. In recent years, there has been a lot of improvement in medical facilities and as a result, the survival rate of the preterm and LBW babies has improved. But at the same time, these neonates with immature immune defenses are exposed to NICU flora for a longer duration. Most of the neonatal septicemia cases now are either LBW or preterm. In the present study, 44% were LBW and 39% were preterm neonates which has led to more LOS (51%) as compared to EOS (49%). Mhada et al. reported 23% of preterm neonates, in their study. Among the maternal risk factors, the difficult delivery (32%) in the form of Caesarean, forceps or vacuum was found much higher risk factor in our study as compared to (14.88%) by Tallur et al.
The bacteriological profile has changed worldwide from predominant Gram-negative to a predominant Gram-positive bacteria isolation.,,,,, Many recent studies have reported the emergence of some new emerging organisms such as CONS, NFGO, and Candida spp. as a cause of neonatal septicemia.,,,,
Our study showed a preponderance of Gram-positive isolates, 60% versus 40%, Gram-negative isolates. Ballot et al., Kaufman and Fairchild and Hoogen et al. reported the isolation of GPB in 54.9%, 68.2%, and 75%, respectively, which is in concordance with the present study.,,
The colonisation of the skin and nasopharynx by CONS and S. aureus in health care workers, overcrowding in nurseries and NICU, and improper hand washing techniques may lead to transmission of Gram-positive organisms in neonates horizontally. There is a predominance of GPB isolation in our study unlike other studies in the North India., The reason could be due to overcrowding in nurseries/NICU and lack of knowledge about infection control measures among health care providers.
Our study showed S. aureus (66%) and CONS (31%) as the most common Gram-positive organisms which is quite high as compared to studies conducted by Agnihotri et al. and Sundaram et al., [Table 2]. NFGO and Klebsiella pneumoniae were the common Gram-negative isolates, which was comparable to the other studies in the region., NFGO tend to colonize and proliferate in nurseries and are transmitted by cross infection.
|Table 2: Bacteriological profile of neonatal septicemia in studies from North India|
Click here to view
Both Gram-positive and Gram-negative isolates showed a high resistance to cephalosporins, penicillin, and amoxyclav in the current study, it was observed that antibiotic resistance among the Gram-positive isolates was highest to penicillin (87%) followed by amoxyclav (66%). Similar reports of high resistance to Ampicillin (71%) were reported by Bhat et al. All the Gram-positive isolates were sensitive to vancomycin similar to a study by Hoogen et al. In the present study, 41% S. aureus isolates were found to be methicillin-resistant, compared to 11.1% reported by Kaistha et al. Gram-negative isolates showed a high resistance to all cephalosporins which is similar to the resistance pattern reported by Agnihotri et al. and Bhat et al.,Klebsiella pneumoniae. showed resistance to all antibiotics tested except imipenem. In our study, the 48% were ESBL producers as compared to 72% as reported by Bhat et al. This high resistance pattern could be attributed to the injudicious use of antibiotics in our region.
In the present study, overall mortality was observed in 11.7%, whereas Chaudhary reported a mortality of 45.5% in their study, which is quite high as compared to our study. This could be attributed to advancement in medical technology and better neonatal care in NICU.
| ~ Conclusion|| |
We want to highlight the fact that Gram-positive organisms particularly S. aureus and CONS are now predominant organisms causing neonatal septicemia in our institution, as well as whole of North India as suggested by studies in past decade [Table 2]. There has been a shift from the predominance of Gram-negative organisms to Gram-positive organisms S. aureus in the past decade throughout the world, the reason for which is not clear.,,,,, Among Gram-negative bacteria (GNB), NFGO are one of the newly emerging groups of organisms with high mortality next only to Klebsiella spp. High resistance to cephalosporins is a cause of concern, as they are one of the most common prescribed antibiotic groups in the region. Urgent need for preventive measures including proper hand washing, barrier nursing, and judicious selection of antibiotics is recommended along with continuous surveillance of the neonatal septicemia.
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Conflicts of interest
There are no conflicts of interest.
| ~ References|| |
Ballot DE, Nana T, Sriruttan C, Cooper PA. Bacterial bloodstream infections in neonates in a developing country. ISRN Pediatr 2012;2012:508512.
Hornik CP, Fort P, Clark RH, Watt K, Benjamin DK Jr, Smith PB, et al.
Early and late onset sepsis in very-low-birth-weight infants from a large group of neonatal Intensive Care Units. Early Hum Dev 2012;88 Suppl 2:S69-74.
Collee JG, Miles RS, Watt B. Tests for the identification of bacteria. In: Collee JG, Fraser AG, Marmion BP, Simmons A, editors. Mackie and McCartney Practical Medical Microbiology. 14th
ed. Edinburgh: Churchill Livingstone; 1996. p. 131-50.
Clinical and Laboratory Standards Institute. Performance Standards for Antimicrobial Susceptibility Testing, Twenty- first Informational Supplement M100-S21. Wayne, PA: CLSI; 2011.
Mhada TV, Fredrick F, Matee MI, Massawe A. Neonatal sepsis at Muhimbili National Hospital, Dar es Salaam, Tanzania; aetiology, antimicrobial sensitivity pattern and clinical outcome. BMC Public Health 2012;12:904.
Tallur SS, Kasturi AV, Nadgir SD, Krishna BV. Clinico-bacteriological study of neonatal septicemia in Hubli. Indian J Pediatr 2000;67:169-74.
Härtel C, Faust K, Avenarius S, Bohnhorst B, Emeis M, Gebauer C, et al.
Epidemic microclusters of blood-culture proven sepsis in very-low-birth weight infants: Experience of the German Neonatal Network. PLoS One 2012;7:e38304.
Cohen-Wolkowiez M, Moran C, Benjamin DK, Cotten CM, Clark RH, Benjamin DK Jr, et al.
Early and late onset sepsis in late preterm infants. Pediatr Infect Dis J 2009;28:1052-6.
West BA, Peterside O. Sensitivity pattern among bacterial isolates in neonatal septicaemia in port Harcourt. Ann Clin Microbiol Antimicrob 2012;11:7.
Kohli-Kochhar R, Omuse G, Revathi G. A ten-year review of neonatal bloodstream infections in a tertiary private hospital in Kenya. J Infect Dev Ctries 2011;5:799-803.
Monjur F, Rizwan F, Asaduzzaman M, Nasrin N, Ghosh NK, Apu AS, et al.
Antibiotic sensitivity pattern of causative organisms of neonatal septicemia in an urban hospital of Bangladesh. Indian J Med Sci 2010;64:265-71.
Darmstadt GL, Saha SK, Choi Y, El Arifeen S, Ahmed NU, Bari S, et al.
Population-based incidence and etiology of community-acquired neonatal bacteremia in Mirzapur, Bangladesh: An observational study. J Infect Dis 2009;200:906-15.
Agnihotri N, Kaistha N, Gupta V. Antimicrobial susceptibility of isolates from neonatal septicemia. Jpn J Infect Dis 2004;57:273-5.
Sundaram V, Kumar P, Dutta S, Mukhopadhyay K, Ray P, Gautam V, et al.
Blood culture confirmed bacterial sepsis in neonates in a North Indian tertiary care center: Changes over the last decade. Jpn J Infect Dis 2009;62:46-50.
Bhat Y R, Lewis LE, Ke V. Bacterial isolates of early-onset neonatal sepsis and their antibiotic susceptibility pattern between 1998 and 2004: An audit from a center in India. Ital J Pediatr 2011;37:32.
Sharma P, Kaur P, Aggarwal A. Staphylococcus aureus
– The predominant pathogen in the neonatal ICU of a tertiary care hospital in amritsar, India. J Clin Diagn Res 2013;7:66-9.
Makhoul IR, Sujov P, Smolkin T, Lusky A, Reichman B, Israel Neonatal Network. Pathogen-specific early mortality in very low birth weight infants with late-onset sepsis: A national survey. Clin Infect Dis 2005;40:218-24.
Kaufman D, Fairchild KD. Clinical microbiology of bacterial and fungal sepsis in very-low-birth-weight infants. Clin Microbiol Rev 2004;17:638-80.
Van den Hoogen A, Gerards LJ, Verboon-Maciolek MA, Fleer A, Krediet TG. Long-term trends in the epidemiology of neonatal sepsis and antibiotic susceptibility of causative agents. Neonatology 2010;97:22-8.
Chaudhary S, Bahl L, Goel A, Sharma DN. Neonatal Septicemia: A Clinico-Bacteriological Study. Thesis, Department of Pediatrics, IGMC Shimla, Himachal Pradesh University; 1989.
Jaswal RS, Kaushal RK, Goel A, Pathania K. Role of C-reactive protein in deciding duration of antibiotic therapy in neonatal septicemia. Indian Pediatr 2003;40:880-3.
Kaistha N, Mehta M, Singla N, Garg R, Chander J. Neonatal septicemia isolates and resistance patterns in a tertiary care hospital of North India. J Infect Dev Ctries 2009;4:55-7.
[Figure 1], [Figure 2]
[Table 1], [Table 2]