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Brief Reports Indian Pediatrics 2002; 39:1034-1039 |
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Clinical and Bacteriological Profile of Neonatal Septicemia in a Tertiary level Pediatric Hospital in Bangladesh |
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Neonatal septicemia remains one of the most important causes of mortality despite considerable progress in hygiene, introduction of new antimicrobial agents, and advanced measures for early diagnosis and treatment(1,2). Reports of the epidemiology of neonatal septicemia from Bangladesh are few. The epidemiological data from other developing countries, however, shows important differences in the incidence, risk factors, pattern and antimicrobial sensitivities of pathogens and mortality from that of developed countries(3-5). Group B streptococcal disease is the most important cause of neonatal sepsis in Europe and North America(6), but there is a preponderance of gram-negative organisms in tropical and developing countries(7). The epidemiology of neonatal septicemia within a geographical location, however, also may change with time(8-9). As neonatal septicemia is a life-threatening emergency and delays in diagnosis and treatment with appropriate antibiotics may have devastating consequences, surveillance is needed to identify the common signs and pathogens of neonatal septicemia as well as the antibiotic sensitivity patterns for the agents of septicemia in a particular area. The purpose of this study was to identify the most common symptoms and signs of neonatal septicemia in our neonatal nursery and the organisms causing these infections along with their antibiotic sensitivity profiles. Patients and Methods Study population: This prospective study was conducted in the neonatal ward of Dhaka Shishu (Children) Hospital in 1998. This is the largest tertiary care pediatric hospital in Bangladesh, and serves primarily an urban poor population. Neonates with suspected septicemia were identified and enrolled by the study physician (ASMNUA), and their inclusion was confirmed by the supervising physician (MAKAC), based on the presence of one or more clinical signs consistent with possible serious bacterial infection (i.e., pneumonia, septicemia, meningitis) including lethargy, refusal of feeds, abdominal distension, vomiting, groaning, grunting, facial grimace, respiratory distress, hypothermia, hyperthermia or sclerema with or without supporting evidence of risk factors such as prematurity, low birth weight (LBW), birth asphyxia, maternal chorioamnionitis (maternal fever and/or foul smelling vaginal discharge) and prolonged rupture of membranes. A thorough history and physical examination was performed and recorded on standard forms. Patients with respiratory distress syndrome (RDS), extreme prematurity (<30 weeks estimated gestational age by Ballard examination), gross congenital anomalies and any previous antibiotic therapy were excluded. Study patients were categorized as having early (within 7 days of life) or late (8 to 28 days of life) onset of signs of septicemia. Blood culture was taken in all cases and lumbar puncture was performed in all cases of suspected meningitis. Table I__Common Clinical Manifestations of the 30 Blood Culture Positive Cases of Neonatal Septicemia
* p = 0.05
Patient management: All cases were initially treated with penicillin and gentamicin or with a third generation cephalosporin in combination with gentamicin depending on severity of illness and prescribing physicians’ preference. This therapy was later modified depending on the identity and antibiotic sensitivity of the isolate from blood/CSF cultures. Other supportive therapy such as correction of acidosis, maintenance of fluid and electrolyte balance, ventilatory assistance, phototherapy and blood transfusion was given as required. Results Among 86 cases of clinically suspected neonatal septicemia, 30 (35%) had a positive blood culture. Blood culture positivity was lower in those with early (26%, 12/46) compared to late-onset (45%, 18/40) disease (P < 0.05). Males with positive blood cultures (63%, 19/30) outnumbered females (37%, 11/30) (p<0.05). More than half of blood-culture-positive cases (60%, 18/30) occurred in LBW (n = 15) or VLBW (n = 3) infants. Half of cases (50%, 15/30) of neonatal septicemia were pre-term, 14 (47%) were term and 1 (3%) was post-term. Blood culture positivity rate was equivalent, however, for preterm (31%, 15/48) and term (38%, 14/37) infants; and for VLBW (27%, 3/11), LBW (36%, 15/42) and normal birth weight (36%, 12/33) infants. More than half of the culture positive neonates were delivered at home (60%, 18/30). Seven culture positive babies (23%) were delivered by caesarean section, and 13 (43%) had a history of birth asphyxia. Neonates with septicemia more often were from low-socio-economic classes (family income < 5000 Taka ($100) per month) (63%, 19/30) than middle (5000 to 10,000 Taka ($100 to 200) (27%, 8/30) or higher income (>10,000 Taka (>$200)(10%, 3/30) groups. Maternal fever during delivery was present in 7% (2/30) of culture positive cases; one mother also had ruptured membranes for more than 24 hours. Table II- Organisms Isolated in 30 Cases of Blood Culture Positive Septicemia in Relation to Onset of Disease, Birth Weight and Gestational Age
The most frequent clinical presentations of patients with culture-proven serious neonatal bacterial infection were respiratory distress (47%, 14/30), lethargy (40%, 12/30), jaundice (40%, 12/30), fever (36%, 11/30) and poor feeding (27%, 8/30) (Table I). Respiratory distress was significantly more common in early-than late-onset septicemia (P < 0.05); presence of other presenting signs was not significantly different in the two groups. Of the 30 organisms isolated, nearly three-fourths (73%, 22/30) were gram-negative bacilli; 8(27%) were gram-positive (Table II). Escherichia coli was the most common organism (30%, 9/30), followed by Klebsiella pneumoniae (23%, 7/30) and Staphylococcus aureus (17%, 5/30). The pattern of organisms isolated was similar, regardless of time of onset of disease, birth weight or gestational age; although S. aureus was isolated from four term infants and just one pre-term baby (Table II). Most E. coli isolates were resistant to ampicillin (89%, 8/9), whereas 78 to 90% of isolates were sensitive to gentamicin, third-generation cephalosporins and ciprofloxacin. In general, approximately half to two-thirds of the other gram-negative isolates were sensitive to gentamicin and the third generation cephalosporins. Most S. aureus isolates were sensitive to cloxacillin (80%, 4/5). Of the 30 culture-positive cases, 12 (40%) died. The neonates who died more often had early (n =8, 66.7%) as opposed to late-onset infection. LBW accounted for 9 (75%) deaths. The case fatality rate was higher in early (67%, 8/12) than late-onset (22%, 4/18) infection (P < 0.05), was inversely related to birth weight ( <1500 g: 66%, 2/3; 1500-2500 g: 47 %, 7/15; > 2500 g: 25%, 3/12), and was highest in neonates infected with Pseudomonas aeruginosa (67%) and Klebsiella pneumoniae (57%) and least in Escherichia coli septicemia (22%). Case fatality was not influenced by gender (males: 37%, 7/19, females: 45%, 5/11). Of the 30 culture-positive cases, 4 also had meningitis with culture-positive CSF; among them, 3 patients (75%) died. Escherichia coli and Pseudomonas aeruginosa caused meningitis in early-onset disease and streptococcus sp. and Staphylococcus aureus in late-onset disease. Discussion In this study at a tertiary-level pediatric hospital in Dhaka, Bangladesh, we found that late-onset neonatal septicemia was more common than early-onset disease, in contrast to other reports in which early-onset septicemia generally has been more common(6,9). Perhaps this discrepancy is due to the fact that mortality in early-onset cases is relatively high(10), as observed in this report, and, thus, some neonates in the catchment area of our hospital, which largely serves a low socioeconomic status community, might have died prior to arrival at the hospital. Although males have been reported to be 2 to 5 fold more likely than females to develop septicemia(10), the nearly 2:1 ratio of male-to-female infants in our study, while seemingly consistent with this data, could also reflect a gender bias in presentation to the hospital for care. Population based studies would be needed to address this important question. The clinical features, culture positivity rates, and case fatality rates, however, were equivalent across gender, suggesting that the males and females in the study overall had a similar degree of illness. The majority of the study population was poor and delivered at home, largely in the hands of untrained birth attendants. Home deliveries are common in Bangladesh(11) and typically are conducted in poor standards of asepsis(12). History of unclean vaginal examination was associated with a 10% incidence of deep infection in one study(13). Home deliveries also are significantly related to birth asphyxia, which was highly prevalent in our study population, and which, in turn, is associated with an increased risk of serious neonatal infection(14). Increased prevalence of gram-negative septicemia, as found in our study, has been reported from other sites in India(7) and Pakistan(10). The prevalence of E. coli may have been due to the fact that it is commonly found as part of the intestinal and vaginal flora, and most deliveries were conducted at home, presumably under conditions of poor hygiene. Group B Streptococcus (GBS) was not isolated in this study, unlike western, developed countries where it is the major agent of neonatal septicemia(6,9). The insignificance of GBS as a pathogen in many developing countries is supported by a number of other studies(15,16). This may be attributable to low prevalence of GBS colonization of pregnant mothers in this area, or, possibly, to the presence of strains with low virulence. For most of the gram-negative organisms, gentamicin and third-generation cephalos-porins were effective(7). In general, the sensitivity of the gram-negative isolates to gentamicin supports continued use of this agent in the initial, empiric treatment of septicemic neonates in our hospital, and also supports WHO recommendations that management of young infants up to age 2 months include parenteral use of benzyl penicillin or ampicillin plus an aminoglycoside such as gentamicin(17). Due to the small sample size and hospital-based design of this study, we recommend additional community-based studies of local patterns and antibiotic sensitivity of pathogens of neonatal septicemia in order to formulate rational antibiotic use policies. There also is a need for community-based case-control studies with larger sample size to identify risk factors and preventive measures for neonatal septicemia. Contributors: ASMNUA collected the data, cared for the patients and prepared the manuscript. MAKAC supervised the data collection, confirmed findings and guided the study. MMH participated actively during enrolment and followup procedures. GLD did the statistical analysis, interpreted the data and finalized the manuscript. ASMNUA shall act as guarantor. Funding: None Competing interests: None stated
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