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 Table of Contents  
Year : 2016  |  Volume : 23  |  Issue : 3  |  Page : 146-151

Neonatal septicaemia, bacterial isolates and antibiogram sensitivity in Maiduguri North-Eastern Nigeria

1 Department of Paediatrics, University of Maiduguri Teaching Hospital, Nigeria
2 Department of Clinical Microbiology, University of Maiduguri Teaching Hospital, Nigeria
3 Department of Pharmacology, University of Maiduguri, Nigeria

Date of Web Publication12-Sep-2016

Correspondence Address:
Simon Pius
Department of Paediatrics, University of Maiduguri Teaching Hospital
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/1117-1936.190340

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Aims and Objectives: The aim and objective of the study was to determine the incidence, bacterial isolates and the antibiogram sensitivity of the isolates in neonates with septicaemia.
Patients and Methods: The neonates with clinical diagnosis of neonatal septicaemia (NNS) were consecutively enrolled into our special care baby unit. The patients were investigated including blood cultures, cerebrospinal fluid cultures and urine among others. Data were analysed with Statistical Package for Social Sciences software version 16.0 (SPSS Inc., Chicago, IL, USA).
Results: Forty-six neonates (42.0%) had a positive blood culture, while 64 (58.0%) were blood culture-negative. Eighteen (39.1%) of those septicaemic neonates with positive blood culture were inborn, while 28 (60.9%) were outborn. The incidence of NNS was 5.9/1000 live births. The male-to-female ratio among septicaemic neonates was 1.9:1. The common risk factors for NNS were prolonged rupture of membrane, prematurity and low socioeconomic status of parents among others. Common clinical features were fever, poor feeding, excessive crying, tachypnoea and hepatomegaly. Staphylococcus aureus 16 (69.6%) and Streptococcus pyogenes 5 (21.8%) were the predominant Gram-positive organisms isolated whereas Escherichia coli 9 (39.1%) and Klebsiella pneumoniae 7 (30.4%) were the predominant Gram-negative organisms isolated. S. aureus was sensitive to cephalosporins and quinolones, but resistant to penicillins. E. coli and K. pneumoniae showed a high resistance (16.7% and 25.6%, respectively) to commonly used aminoglycoside such as gentamycin.
Conclusion: The burden of NNS was high with high mortality in the study centre. The sensitivity pattern had remarkably changed; however, a combination of cephalosporins such as cefuroxime and gentamycin is still a good option.

Keywords: Antibiotics, bacterial pathogen, neonate, outcome, sensitivity, septicaemia

How to cite this article:
Pius S, Bello M, Galadima GB, Ibrahim HA, Yerima ST, Ambe JP. Neonatal septicaemia, bacterial isolates and antibiogram sensitivity in Maiduguri North-Eastern Nigeria. Niger Postgrad Med J 2016;23:146-51

How to cite this URL:
Pius S, Bello M, Galadima GB, Ibrahim HA, Yerima ST, Ambe JP. Neonatal septicaemia, bacterial isolates and antibiogram sensitivity in Maiduguri North-Eastern Nigeria. Niger Postgrad Med J [serial online] 2016 [cited 2021 Jan 27];23:146-51. Available from: https://www.npmj.org/text.asp?2016/23/3/146/190340

  Introduction Top

Neonatal septicaemia (NNS), despite recent advances in hygienic practices in hospitals and introduction of potent antibiotics, has remained a major cause of morbidity and mortality worldwide, with a severe magnitude in a poor resource setting.[1] The incidence of NNS varies widely between the developed countries and developing countries and also varies from one nursery to another. The characteristics of neonates studied also influence the incidence. For example, the prevalence rate is 3–10-fold higher in preterm than in full-term neonates.[2] In addition, the incidence is higher in low birth weight (LBW) than normal weight neonates, and in males than females.[3],[4],[5],[6] The incidence of NNS varies from 0.3 to 3/1000 live birth (LB) in Europe,[7] 1–4/1000 LB in North America [8] and Khalid [9] reported the case fertility rate range between 2% and 50% in Asia, while Yoon et al.[10] reported an incidence of 10.5%. However, contrary to these preceding reports, the reported incidence from different parts of Nigeria ranged from 5.5 to 54.9/1000 LB.[11],[12]

The early features of NNS are frequently subtle and non-specific, such as poor sucking ability, apnoea, bradycardia, respiratory distress, diarrhoea, vomiting abdominal distension, jitteriness, seizures and jaundice.[8],[9],[10],[11],[12],[13] The common risk factors of NNS include prematurity, prolonged rupture of membrane (PROM), maternal toxaemia, precipitous labour and maternal infection.[4],[8],[9],[10],[11],[12],[13],[14] NNS is a life-threatening emergency, and delay in prompt diagnosis and early starting of appropriate antibiotics may have devastating complication.[10],[11] The gold standard for the diagnosis of NNS is the use of blood culture for the identification of common aetiological organisms of NNS, and antibiotic susceptibility profile of the pathogens is critical.[15] A prospective study to identify bacterial pathogens and their antibiogram sensitivity in a regional tertiary health facility, the University of Maiduguri Teaching Hospital (UMTH), was carried out.

  Patients and Methods Top

This is a prospective descriptive study which was carried out in the special care baby unit (SCBU), UMTH, Maiduguri. It comprised all neonates admitted to the SCBU who were at risk for sepsis or had presumptive diagnosis of NNS based on the presence of fever, poor feeding, respiratory difficulty and hypothermia or history of PROM >18 h, peripartum fever, history of urinary tract infection (UTI) in the mother as well as preterm labour for a period of 12 months from 1st January to 31st December 2012. The inclusion criteria were (1) preterm/term neonates with clinical features suggestive of NNS, (2) presence of maternal perinatal risk factors for septicaemia such as maternal peripartum pyrexia and PROM, (3) history of unclean delivery and poor cord care and (4) caregiver/mother consenting. While exclusion criteria were (1) maternal peripartum antibiotic administration, (2) prior antibiotic use in the child within 72 h before presentation and (3) gross congenital malformation/surgery. A total of 110 neonates were recruited after meeting the criteria for screening for NNS. The demographic characteristics and data were entered into a standard pro forma; these include, age, sex, place of antenatal care/delivery, maternal risk factors for NNS; such as maternal peripartum fever, history of PROM, history of delivery at home, delivery in traditional birth attendant (TBA) house, perinatal asphyxia, prematurity and poor cord care among others. Clinical features of sepsis in the child such as fever, poor sucking activity, respiratory distress, evidence of hyper/hypopyrexia and convulsion were all documented.

Ethical clearance was obtained from the UMTH Research and Ethics Committee, while consent to voluntary participation in the study was obtained from the parents/caregivers after obtaining an informed consent. The samples collected include blood, cerebrospinal fluid (CSF), urine, aspirates and swabs from discharging sites. Blood for culture was taken from a peripheral vein (antecubital fossa or dorsum of the hand) using a 21-gauge scalp vein needle after thorough skin preparation with the application of 2% iodine tincture and followed by cleansing with 70% alcohol solution. Two culture bottles containing 12 ml of culture media - brain–heart infusion was inoculated aseptically with at least 2 ml of blood each [1],[16] and immediately incubated at 37°C for 18–24 h. Each specimen was examined twice a day for growth. Turbidity in the culture bottles and/or excess production of gas with signs of haemolysis indicates bacterial growth. It was subcultured on blood agar using sheep blood and/or MacConkey agar on days 2, 3, 5, 7 and 10, and this was incubated at 37°C for 18–24 h. Further, identification of the pathogens was done based on the agar culture plate, and the colonial morphology was described for the specific pathogens (size, colour, texture and elevation). Gram-staining was done, and from the Gram reaction, the organisms were classified as either Gram-positive or Gram-negative. For Gram-positive organisms, further biochemical tests such as catalase and coagulase were done. While for the Gram-negative identification, motility tests and other biochemical tests such as oxidase test, indole, citrate, urease and Kligler iron agar were done. The sensitivity pattern of the organisms was carried out against the common antibiotic discs provided by the investigator using disc diffusion method according to the Clinical and Laboratory Standard Institute.[16] CSF samples were collected by lumbar puncture between the 4th and 5th spinal arachnoid space after adequate skin preparation with the application of 2% iodine tincture followed by cleansing with 70% alcohol solution. Urine samples were obtained by suprapubic aspiration after ensuring that the neonate had not voided in the preceding 30 min to 1 h. All the samples obtained as indicated were cultured appropriately. The results and clinical outcome were recorded in the pro forma. The recorded data were analysed using Statistical Package for Social Sciences software version 16.0 (SPSS software Inc., Chicago, IL, USA). Tables were used for data presentation as appropriate. Associations were tested using Chi-square test. Statistical significance was set at P < 0.05.

  Results Top

Seven hundred and twenty-three neonates were admitted into the SCBU during the study period, and of these, 377 (52.1%) were outborn, whereas 346 (47.9%) were inborn. One hundred and ten (15.2%) neonates admitted met the inclusion criteria and were enrolled into the study. Seventy-three (66.0%) were males and 37 (34.0%) were females giving a male-to-female ratio of 1.9:1. Forty-two (38.2%) of the 110 neonates were inborn and 68 (61.8%) were outborn, and the age of the neonates at admission ranged from 0 to 28 days with a mean of 5.33 ± 5.29 days. Forty-nine (44.5%) neonates presented within th first 72 h of life, while 61 (55.5%) presented after 72 h of life. Eighteen (16.4%) newborns were preterm while 92 (83.6%) were full term.

The weight at admission ranged between 1150 and 4300 g with a mean weight of 2842.27 ± 734.23 g. Forty-six (41.8%) newborns who were studied had blood culture-positive septicaemia, of whom 18 (39.0%) were inborn and 28 (61.0%) were outborn. The remaining 64 (58.2%) had a negative blood culture. Early onset NNS (EOS) accounted for 22 (47.8%) and the remaining 24 (52.2%) were late onset NNS (LOS). The characteristics of the isolates recovered from blood cultures in EOS were Escherichia coli 7 isolates, Staphylococcus aureus 2, Klebsiella pneumoniae 7, Coliform species 5 isolates and Haemophilus influenzae one isolate. The isolates in LOS were S. aureus with 10 isolates, Streptococcus pyogenes with 5 isolates, E. coli with 2 isolates, K. pneumoniae with 2 cases and H. influenzae, Staphylococcus epidemidis, Streptococcus pneumoniae, Salmonella spp. and Coliforms had one isolate each.

The comorbidities in EOS include ten cases of asphyxia, two cases of conjunctivitis, two cases of tetanus, six cases of UTI and two cases of pustular abscess. One case asphyxiated that E. coli EOS died and one case of Coliform EOS also died, making the two death cases in EOS and all the two were preterm male neonates. The comorbidities in LOS are as follows: four cases of S. aureus septicaemia had tetanus, one case of S. aureus with asphyxia, two cases with omphalitis and three cases with UTI, in which S. aureus was positive. There were two cases of S. pyogenes septicaemia with asphyxia, two cases of E. coli septicaemia with meningitis, two cases of LOS K. pneumoniae septicaemia with perinatal asphyxia, a case of H. influenzae with omphalitis and a case of Coliform septicaemia with tetanus. There were two deaths in EOS, one case of E. coli with perianal asphyxia and one case of Coliform with omphalitis. Among the LOS septicaemia isolates, there were two deathsof E. coli septicaemia, three deaths of S. aureus, two deaths of S. pyogenes, two deaths from K. Pneumoniae and H. influenzae. There were two preterm deaths among the LOS while the remaining nine death cases were term. Out of the ten preterms, four died while nine out of the 36 terms died, and overall, there were five deaths among Gram-positive isolates and nine deaths among Gram-negative isolates, giving a mortality rate of 28.2% (13/46). During the study period, the total number of births at the labour ward was 3050, giving an incidence of NNS among all inborn neonates (i.e., delivered at UMTH) of 5.9/1000 live births.

[Table 1] shows microbial isolates. There were equal distributions of both Gram-positive and Gram-negative agents isolated from the blood culture, 23 (50.0%) each. The predominant Gram-positive isolate was S. aureus accounting for 16 (69.6%) isolates. S. pyogenes, Streptococcus pneumonia and Staphylococcus epidermidis accounted for 21.8%, 4.3% and 4.3%, respectively. E. coli was the predominant Gram-negative organism isolated in 9 (39.1%) neonates, closely followed by K. pneumoniae in 7 (30.4%) while 5 (21.8%) isolates were Coliforms.
Table 1: Frequency of pathogens isolated among 46 neonates with a positive blood culture

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[Table 2] shows the associated morbidities. There were 12 cases of tetanus neonatorum, 5 (41.7%) of whom had a positive blood culture, and of these, four died and one left against medical advice. Ten had UTI, of which 3 (30.0%) had positive blood culture and two died. There were 11 cases of omphalitis, of whom 7 (63.6%) had a positive blood culture with no death recorded. There were two cases each of abscess and conjunctivitis; none of these, however, had a positive blood culture. Six neonates had meningitis and only two (33.0%) were blood culture-positive and both died. There were ten neonates with birth asphyxia, 8 (80%) had a positive blood culture and four died.
Table 2: Other morbidities associated with septicaemia

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[Table 3] shows the pattern of in vitro sensitivity of the Gram-positive isolates, S. aureus was (100%) sensitive to cefuroxime, augmentin, ceftriaxone, ceftazidime, ofloxacin, cephalexin, pefloxacin and nalidixic acid. It also maintained a significant sensitivity to gentamycin (70%). However, it had reduced sensitivity to norfloxacin (50%) and amoxicillin (64.3%). S. epidermidis was (100%) sensitive to all the antibiotics tested against it, which included amoxicillin, gentamycin, ciprofloxacin, streptomycin, chloramphenicol and levofloxacin. S. pyogenes were (100%) sensitive to cefuroxime, ceftriaxone, ceftazidime, ofloxacin, nalidixic acid, levofloxacin and cotrimoxazole, with reduced sensitivity to chloramphenicol (40%), amoxicillin (50%), streptomycin (50.0%), ampiclox (60.0%) and rifampicin (60%). S. pneumoniae was (100%) sensitive to all the antibiotics against which it was tested, which include ampiclox, cefuroxime, amoxicillin, ceftriaxone, gentamycin, ciprofloxacin, rifampicin and levofloxacin.
Table 3:Gram-positive isolates and their antibiotic sensitivity rates

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[Table 4] shows the sensitivity pattern of the Gram-negative bacteria isolates. E. coli was 100% sensitive to ampiclox, ceftriaxone, ceftazidime, ciprofloxacin, ofloxacin, chloramphenicol and levofloxacin; however, its sensitivity to gentamycin was 83.3%. It had reduced sensitivity to ampicillin (25.0%), cephalexin (33.3%) and augmentin and amoxillin was 50% each. Klebsiella spp. isolated had 100% sensitivity to ampiclox, ceftriaxone, ceftazidime, erythromycin, norfloxacin, chloramphenicol and levofloxacin. Its sensitivity to streptomycin was 87.5% and to pefloxacin was 85.7%, but had reduced sensitivity to augmentin (14.3%), ampicillin (20.0%), gentamycin (25.6%) and cotrimoxazole (28.6%).
Table 4: Gram-negative bacteria and their antibiotic sensitivity rate

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The Coliforms isolated were 100% sensitive to augmentin, ceftriaxone, gentamycin, ciprofloxacin, ofloxacin and pefloxacin. Salmonella typhi was sensitive to all the antibiotics against which it was tested such as augmentin, ceftriaxone, gentamycin, ciprofloxacin, ofloxacin, streptomycin, pefloxacin and nalidixic acid. H. influenzae was sensitive to all the antibiotics to which it was tested; such antibiotics include cefuroxime, augmentin, ceftriaxone, gentamycin, ciprofloxacin and pefloxacin. There were two deaths (9.09%) out of 22 cases of EOS. One death was due to Coliforms spp. and the other was due to E. coli. There were 11 deaths (45.83%) out of 24 cases of LOS, three deaths due to E. coli septicaemia (two deaths had E. coli meningitis), three deaths were due to S. aureus, two deaths were due to S. pyogenes and K. pneumoniae and one patient who had H. influenzae septicaemia died.

  Discussion Top

This study has further buttressed the fact that NNS is an important cause of morbidity and mortality among the sick neonates.[1] The incidence of NNS of 5.9/1000 live births in this study was higher compared to those reported from developed countries,[1],[7],[10] although it was lower than the incidence reported in some studies from South-Western Nigeria.[11],[15] The bacterial isolation rate of 42% in this study was higher than the previous report from the same centre.[1] However when compared to other studies within the country by Anah et al.[12] (60%) was low but similar to finding by Meremikwu et al.[17] (45.9%). Some studies from Africa such as that from Uganda (37%) was lower than our finding, while that from Ivory Coast (65.2%),[18],[19] was higher than our finding. The bacterial isolation rate of 42% in our finding was much higher than that from Bangladesh (34.8%)[20] and that by Huda et al.[21] from Kuwait (8.7%).

All the isolates in this study were monomicrobial, and have been implicated previously in NNS.[6],[12] The predominant organisms include S. aureus, S. pyogenes among the Gram-positive agents and E. coli, K. pneumoniae among the Gram-negative agents in this study that had been reported by other workers in Nigeria.[1],[22],[23],[24] Other organisms were S. epidemidis and S. pneumoniae among the Gram-positive bacteria and Coliforms, H. influenzae and Salmonella spp. among the remaining Gram-negatives. However, there were equal proportion of both Gram-positive and Gram-negative organisms in this study which differs with findings in the previous report from the same centre which showed Gram-positive organisms as the predominant,[1] similar to other studies in Nigeria.[22],[23],[24],[25] In addition, in this study, among the Gram-negative organisms, E. coli was more common than K. pneumoniae. This differs from an earlier report by Ambe et al.,[1] in which Klebsiella spp. was the predominant Gram-negative pathogen. This affirms the well-known phenomenon of periodic changes in the pattern of bacterial pathogens of NNS in a given environment over time, but differs from report from other centres in Nigeria.[26]

Majority of patients with S. aureus septicaemia had late onset septicaemia and were among the outborns, suggesting that the infection may be community-acquired. This favourably compares with the previous reports from Nigeria.[1],[3],[6] The role of Gram-positive bacteria in NNS is well known, particularly among neonates with late onset septicaemia. This is related to the predominance of S. aureus in the blood stream of outborn babies, thus highlighting the role of the community in the acquisition of Gram-positive bacteria. This could be associated with unhygienic birth practices among some of the TBAs and other caregivers of newborns in the community, who might be harbouring these organisms in their hands and nostrils and they may also employ unhygienic methods in delivery.[12] E. coli and other Coliforms are predominant in the early onset NNS and largely among the inborn neonates.[23] The explanation for the predominance of Gram-negative bacteria in early onset NNS in this study could be related to the colonisation of the birth canal by Gram-negative enteric bacilli which lead to ascending infection following chorioamnionitis in the presence of PROM or during passage of the baby through the birth canal at delivery.[22],[26] These findings support other studies from Nigeria and other developing countries.[11],[22] However, it differs from the reports from Germany and other parts of the developed world.[1],[27]

The antibiogram pattern of the isolates revealed a decreasing sensitivity to the commonly used antibiotics, especially those of the penicillin groups. S. aureus has remained sensitive to augmentin, and to the second and third generation cephalosporins such as cefuroxime, ceftriaxone and ceftazidime. It is also highly sensitive to quinolones such as ofloxacin, pefloxacin, levofloxacin, ciprofloxacin and norfloxacin. However, the use of quinolones in newborns is discouraged due to the fear of potential damage to the growth plates of the growing bones.[28] The sensitivity of this organism to drugs such as ampiclox, amoxicillin, gentamycin, erythromycin and chloramphenicol has significantly decreased. Chloramphenicol is not routinely used in NNS because of its associated grey baby syndrome.[1],[28] The explanation for the cephalosporins retaining their effectiveness may be due to the fact that they are less frequently used antibiotics except in severe infections and also their prohibitively high cost may contribute to their infrequent use by the community, thereby reducing drug pressure that usually lead to the development of resistance. Sensitivity to gentamycin has also decreased probably because gentamycin is used as a first-line drug in most combination with other antibiotics. However, it is a drug used for the treatment of gonorrhoea and can be easily purchased as over-the-counter drug.

The only case of S. epidermidis isolated was sensitive to all the antibiotics to which it was tested. The reason for this high sensitivity rates may be due to the fact that it is not a common organism in NNS and so, drug pressure is less. S. pyogenes was sensitive to cephalosporins as well as quinolones; however, it was resistant to penicillins, similar to a previous report.[29] The good activity of nalidixic acid and cotrimoxazole may be due to the fact that these drugs are no longer routinely used and so they may have regain their potency to some of the organisms following a decrease in routine use. S. pneumoniae was sensitive to all the drugs against which it was tested. Unlike the Gram-positive organisms, the Gram-negative organisms had significantly reduced sensitivity to a good number of antibiotics against which they were tested. E. coli being the predominant Gram-negative organism isolated had a reduced sensitivity to penicillins. Klebsiella spp., the second most prevalent Gram-negative organism isolated, had reduced sensitivity to augmentin, cephalexin, ampicillin, cefuroxime, gentamycin, cotrimoxazole, amoxicillin and ciprofloxacin, but it has maintained a good sensitivity to levofloxacin and norfloxacin. This is expected because these drugs are expensive and are not commonly used in the community, also not used in the neonatal unit.[28]

Coliforms were sensitive to most of the antibiotics against which they were tested except for reduced sensitivity to cefuroxime, nalidixic acid and cephalexin. H. influenzae and Salmonella spp. were sensitive to all antibiotics against which they were tested, mainly the cephalosporins and the quinolones. The reason probably being an expensive drug which prohibits routine use in clinical practice, thereby making them retain their potency. This finding is similar to other reports from Nigeria.[29],[30] There were eight deaths due to Gram-negative bacteria, out these, 4 were preterm LBW neonates, which was similar to the report from one centre in Nigeria.[30] Four deaths were due to E. coli infection, of these, two cases of E. coli were also isolated from CSF. There were two deaths due to Klebsiella pneumonia and one death each from H. influenzae and Coliforms. The remaining five deaths were due to Gram-positive. The overall mortality in this study was 13/46 (28.3%) which was high. However, it was lower than the mortality reported elsewhere in Nigeria.[30] It can be proffered that infections with Gram-negative organisms have an increased mortality, also in the presence of comorbidities such as UTI, meningitis and tetanus among others further increased the mortality rates. These findings are similar to reports from other parts of Nigeria.[21],[22],[30]

  Conclusion Top

This study has further highlighted several important issues in NNS. The incidence of NNS is still high in this environment with an equally high mortality. The prevalent pathogens in our study differed from that in the developed countries with GBS and S. aureus predominating, while S. aureus and E. coli were predominant in developing countries; however, in our finding, there was reversal among Gram-negative pathogens, as E. coli predominated placing Klebsiella pneumonia as the second predominant Gram-negative pathogens of NNS with reduced sensitivity to cefuroxime and gentamycin, contrary to the finding in a retrospective audit of NNS conducted in the same centre 5 years earlier.

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  References Top

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  [Table 1], [Table 2], [Table 3], [Table 4]

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