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Year : 2018  |  Volume : 2  |  Issue : 2  |  Page : 152-155

Clinical features and outcomes of pneumococcal bacteremia among children at a tertiary care hospital

1 Department of Pathology and Laboratory Medicine, Aga Khan University, Karachi, Pakistan
2 Department of Pediatrics and Child Health, Aga Khan University, Karachi, Pakistan
3 Department of Pathology and Laboratory Medicine; Department of Pediatrics and Child Health, Aga Khan University, Karachi, Pakistan

Date of Web Publication14-Jun-2018

Correspondence Address:
Dr. Sadia Shakoor
Department of Pathology and Laboratory Medicine, Department of Pediatric and Child Health, Aga Khan University Hospital Karachi
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/bbrj.bbrj_15_18

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Background: Invasive pneumococcal disease (IPD) has high mortality among children. Pneumococcal bacteremia is an important marker of IPD but has received limited attention in predicting the outcomes of illness. The aim of this study was to evaluate clinical features, focus of infection, and comorbid of pneumococcal bacteremia in a pediatric cohort at a tertiary care center in Karachi, Pakistan. Methods: Children aged 0–14 years admitted to the Aga Khan University Hospital with pneumococcal bacteremia were identified through a laboratory database. Demographic, clinical, and outcome data were obtained from patients' medical records. Data entry and analysis were carried out in MS Excel and SPSS version 19.0. Results: Forty (n = 40) episodes of pneumococcal bacteremia in 39 children were identified. The median age of the cohort was 2.5 (interquartile range 4.15–1.1) years; 30% (n = 12) of these were infants aged 0–12 months. The primary focus of infection was identified as pneumonia in 47.5% (n = 19) and meningitis in 7.5% (n = 3). The prevalence of occult bacteremia was 27.5% (n = 11). Outcomes of infection at hospital discharge were assessed in 31 patients as nine patients were either transferred out or left against advice. Of 31 patients, 6 (19.4%) died and 25 (80.6%) were discharged home. Associations with mortality included sepsis (P = 0.017) and absence of a focus (occult bacteremia) (P = 0.007). Conclusion: Sepsis and occult bacteremia (without an underlying focus) were associated with mortality. No association was found between choice of antibiotics administered, penicillin minimum inhibitory concentration, and poor outcome at discharge. Other factors such as comorbidities, immune status, and focus of infection play an important role in predicting the outcomes of pneumococcal bacteremia.

Keywords: Occult pneumococcal bacteremia, pediatric, pneumococcal bacteremia, sepsis

How to cite this article:
Fatima T, Malik F, Khan E, Mir F, Shakoor S. Clinical features and outcomes of pneumococcal bacteremia among children at a tertiary care hospital. Biomed Biotechnol Res J 2018;2:152-5

How to cite this URL:
Fatima T, Malik F, Khan E, Mir F, Shakoor S. Clinical features and outcomes of pneumococcal bacteremia among children at a tertiary care hospital. Biomed Biotechnol Res J [serial online] 2018 [cited 2022 Oct 2];2:152-5. Available from: https://www.bmbtrj.org/text.asp?2018/2/2/152/234451

  Introduction Top

Streptococcus pneumoniae, an encapsulated, Gram-positive coccoid bacterium, is the leading cause of community-acquired pneumonia, bacterial meningitis, and bacteremia globally in children and adults. It is also an important cause of sinusitis, otitis media, septic arthritis, osteomyelitis, and peritonitis. The incidence of pneumococcal disease is highest in infants, <2 years, and in elderly population over 60 years of age.[1] The World Health Organization estimated in 2005 that more than 1.6 million deaths occur annually due to pneumococcal infections, majority of which are seen in children under 5 years (0.7–1 million), and among those residing in developing countries.[2] In 2013, more than 7.5 million cases of pneumococcal meningitis were recorded, which is significantly higher than the prevalence of other bacterial meningitides.[3] With the introduction of pneumococcal conjugate vaccines (PCV-10 and PCV-13), a reduction in rates of pneumococcal infections is expected globally, with greatest impact on the rates of invasive disease.

Invasive pneumococcal disease (IPD), often indicated by the presence of pneumococcal bacteremia, is a major public health concern in developing countries due to its high morbidity and mortality.[2] Due to unavailability of sufficient local data, clinical burden and outcomes of both IPD and pneumococcal bacteremia are under-appreciated in Pakistan.[4] Children hospitalized with pneumococcal bacteremia are a crucial population to be characterized for signs, symptoms, and outcome of illness. We have analyzed episodes of pneumococcal bacteremia in a pediatric cohort evaluated at a tertiary care hospital in Karachi, Pakistan, to inform possible risk factors and their impact on outcome.

  Methods Top

We conducted a hospital-based retrospective review of medical records to derive a database containing clinical information on pediatric pneumococcal bacteremia. An episode-centric cohort was created in a laboratory database, through identification of children aged 0–14 years hospitalized at the Aga Khan University Hospital, from January 2012 to December 2014, with blood cultures positive for S. pneumoniae.

A case of pneumococcal bacteremia was defined as an occurrence of IPD confirmed by positive blood culture for S. pneumoniae from a hospitalized patient. Microbiologically, pneumococci isolated from blood cultures were identified through optochin sensitivity and bile solubility tests.[5] Susceptibility testing was performed for penicillin with E-test (bioMereiux, France) to determine minimum inhibitory concentrations (MICs) and by the disk diffusion method for all other antibiotics with breakpoints recommended in the Clinical Laboratory Standard Institute M100 document.[6]

Medical records of all identified patients admitted during the study period of 3 years were reviewed for clinical parameters at admission (including presence of sepsis), primary foci of infection, comorbid, duration of hospital stay, antibiotics administered in first 48 h, and hospital stay outcomes (stable discharge, death, or loss to follow-up). All clinical and laboratory data were entered and analyzed in MS Excel and exported to SPSS version 19.0 (IBM, Armonk, Newyork, USA) for statistical analyses. To determine predictors of death as an outcome, bivariate analysis was performed using Fisher's exact test. Comparisons of median values were carried out using Mann–Whitney U-test.

The study protocol was reviewed approved by the Aga Khan University Ethical Review Committee (ERC # 4137-Pat-ERC-16).

  Results Top

We identified 40 episodes of pneumococcal bacteremia in 39 pediatric patients seen in the hospital from 2012 to 2014. Male to female ratio in the cohort was 1.35. The median age of the cohort was 2.5 (interquartile range [IQR] 4.15–1.1) years; 30% (n = 12) of patients were infants aged 0–12 months.

The median duration of symptoms before presentation was 4.5 (IQR 7–1) days. Duration of illness was shorter among those presenting with occult bacteremia than those with an underlying focus, but this difference was not statistically significant (median 1 day vs. 5 days, P = 0.19). The most common presenting symptom was fever, with localizing symptoms seen (headache or seizures for meningitis; cough and dyspnea for pneumonia) in 72.5% (n = 29). No localizing signs or symptoms were found in 27.5% (n = 11). None of the children in the cohort had received any doses of the pneumococcal vaccine.

Chest radiographs were performed in 75% of episodes (n = 30) with signs of pneumonia (consolidation or new infiltrates) observed in 16 of 30 patients (53%). Central nervous system imaging studies were performed in 17.5% (n = 7) with radiological signs consistent with meningitis in two patients (28.6%). Concomitant cerebrospinal fluid and/or sputum cultures were performed in 10% (n = 4) episodes. The median duration of hospital stay was 3 days (IQR 5.75–2; range 1–16). Median hospital stay was longer in patients with occult bacteremia (5 days vs. 2 days in those with a focus, P = 0.07; Mann–Whitney U-test). Underlying conditions and comorbid among the 39 patients are shown in [Figure 1].
Figure 1: Proportion of underlying illnesses among children with pneumococcal bacteremia (n = 39). Endocrine/metabolic (diabetes insipidus and renal tubular acidosis; n = 1 each); hematological/immunological (Bruton's agammaglobulinemia and thalassemia major; n = 1 each); infectious (HIV and acute measles; n = 1 each); leukemia (acute lymphoblastic leukemia); chronic liver disease not otherwise specified and markers for hepatitis A, B, C, D, and E negative; autoimmune (juvenile rheumatoid arthritis and autoimmune hemolytic anemia [AIHA]; 1 each). The child with AIHA had two episodes of pneumococcal pneumonia 1 year apart (survived both episodes). Trauma refers to mandibular fracture due to fall from height 6 months before illness

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The underlying focus of infection and clinical outcomes of the 40 episodes are shown in [Table 1]. The overall mortality rate in the cohort was 15% (n = 6).
Table 1: Focus of pneumococcal infection and outcomes in the 40 episodes of pneumococcal bacteremia

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Penicillin susceptibility performed on pneumococci showed MICs to be <0.06 μg/mL (sensitivity cutoff for meningitis; intravenous penicillin G) in 47.5% (n = 19) and 0.12–1 μg/mL in 52.5% (n = 21). MICs of more than 1 μg/mL were not observed. Susceptibility testing results against other antibiotics showed the following resistance rates: 45% resistant to erythromycin (n = 18), 82.5% against cotrimoxazole (n = 33), 5% against ofloxacin (n = 2), and 12.5% against chloramphenicol (n = 5).

All patients received appropriate therapy within 6 h of presentation. Intravenous ceftriaxone was the most commonly administered antibiotic, given in 23 episodes (57.5%), while ampicillin/amoxicillin, meropenem, or piperacillin was used in 6, 5 and 3 episodes, respectively. Two patients received oral azithromycin as primary therapy and were not prescribed a beta-lactam (both survived and one had an upper respiratory tract infection, while the other presented with pneumonia).

Correlation of risk factors and characteristics with mortality was performed on 31 evaluable episodes (as patients were either transferred out for care to another center or left against medical advice in nine instances). Bivariate analysis showed a significant association between sepsis and mortality (P = 0.017) and between occult bacteremia (without focus) and mortality (P = 0.007). There was no association of mortality with sex, presence of meningitis, penicillin MIC of >0.06 μg/mL, or presence of an underlying comorbid.

  Discussion Top

This hospital-based case surveillance study provides valuable estimates of the characteristics and outcome of pneumococcal bacteremia among children in the local setting. Pneumonia remained the most common underlying focus. Penicillin susceptibility results or the choice of antibiotic was not associated with death. Sepsis, indicating the severity of illness, and occult bacteremia were associated with mortality. A small sample size precluded multivariate analysis to determine independent associations of risk factors with mortality.

In this study, we observed a lack of vaccination history among children with pneumococcal bacteremia. The PCV-10 was introduced as part of the Expanded Program for Immunization in 2013.[7] Our study period, therefore, encompasses the vaccine introduction phase. The conjugate vaccine has been shown to be useful in preventing infections resembling occult pneumococcal bacteremia (OPB).[8] Studies of the incidence of pneumococcal bacteremia in subsequent years will be important to inform the impact of PCV-10.

We also found a high prevalence of OPB in our cohort. OPB has previously been observed to have a higher prevalence in retrospective reviews than in prospective evaluations of pneumococcal bacteremia.[9] This may be due to case selection bias in some prospective cohorts, but the reason remains unknown. Higher prevalence of OPB should alert pediatricians performing emergency room assessments to the possibility of pneumococcal illness in children presenting with unlocalized fever in this setting. Of even greater concern is the association of mortality with OPB in our cohort. Although there was no greater delay in administering appropriate antibiotic treatment to these children, no predilection for greater severity/sepsis, and the duration of illness before presentation was in fact shorter for OPB, there are probably other factors associated with OPB that increased the risk for poor outcomes. Perhaps, administration of ancillary treatments such as chest physiotherapy for pneumonia, aggressive management of meningitis, and spontaneous bacterial peritonitis (SBP) undertaken in children with a focus of infection also improves outcomes and such ancillary modalities are not employed in OPB. A better understanding of outcomes of OPB is imperative through multicenter studies.

The most common underlying illnesses in the cohort were nephrotic syndrome and biliary atresia. Both diseases have been associated with pneumococcal illness and IPD.[5],[10],[11] Chronic liver disease was also identified in two patients, suggesting a further association of disturbance of biliary function on IPD. Patients with severe liver disease have increased morbidity and mortality due to pneumococcal infections, and vaccination is mandatory before undertaking hepatic transplantation.[12] Pneumococcal SBP is a recognized complication in individuals with nephrotic syndrome, with a mortality rate of 1.5%,[13] attributed to impaired complement-dependent opsonization in these patients, delaying clearance of encapsulated S. pneumoniae. High prevalence of these underlying illnesses in our hospital cohort suggests that early pneumococcal vaccination should be considered in children with these diseases to avoid IPD.[14]

Our study has limitations. Blood cultures have a low yield for pneumococci in IPD,[15] and therefore, outcomes we present are not reflective of nonbacteremic IPD. Second, serotyping was not performed on pneumococcal isolates in our study. Predictors of mortality could also not be determined in a multivariate model due to the small sample size of the cohort.

  Conclusion Top

Our results from 40 pediatric pneumococcal bacteremia episodes demonstrate that pneumonia was the most common underlying infection. Our results also suggest that presence of sepsis warrants aggressive management as it is associated with poorer outcomes. Moreover, occult bacteremia should be recognized early through developing clinical tools to identify children at risk, especially in view of the higher mortality associated with this entity in our cohort. Multicenter studies of pediatric cohorts with IPD should be undertaken to determine the risk factors and predictors of poorer outcomes and to assess the impact of the conjugate vaccine on this illness.

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Conflicts of interest

There are no conflicts of interest.

  References Top

Pilishvili T, Lexau C, Farley MM, Hadler J, Harrison LH, Bennett NM, et al. Sustained reductions in invasive pneumococcal disease in the era of conjugate vaccine. J Infect Dis 2010;201:32-41.  Back to cited text no. 1
O'Brien KL, Wolfson LJ, Watt JP, Henkle E, Deloria-Knoll M, McCall N, et al. Burden of disease caused by Streptococcus pneumoniae in children younger than 5 years: Global estimates. Lancet 2009;374:893-902.  Back to cited text no. 2
Vos T, Barber RM, Bell B, Bertozzi-Villa A, Biryukov S, Bolliger I. Global, regional, and national incidence, prevalence, and years lived with disability for 301 acute and chronic diseases and injuries in 188 countries, 1990-2013: A systematic analysis for the Global Burden of Disease Study 2013. Lancet 2015;386:743-800.  Back to cited text no. 3
Shakoor S. The paediatric pneumonia conundrum in our population: Initial steps towards understanding the epidemic. Pak J Med Res 2014;53:74-5.  Back to cited text no. 4
Janoff EM, Musher DM. Streptococcus pneumoniae. In: Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases, Updated Edition. Vol. 8 2014. p. 2310-27.e5.  Back to cited text no. 5
Clinical and Laboratory Standards Institute. Performance Standards for Antimicrobial Susceptibility Testing: Twenty-Third Informational Supplement. CLSI document M100-S23. Wayne, Pennsylvania USA: Clinical and Laboratory Standards Institute; 2013.  Back to cited text no. 6
Shakoor S, Kabir F, Khowaja AR, Qureshi SM, Jehan F, Qamar F, et al. Pneumococcal serotypes and serogroups causing invasive disease in Pakistan, 2005-2013. PLoS One 2014;9:e98796.  Back to cited text no. 7
Laaksonen N, Rintamäki L, Korppi M. Pneumococcal vaccinations effectively prevent blood culture-negative infections that resemble occult pneumococcal bacteraemia or bacteraemic pneumococcal pneumonia at one to 36 months of age. Acta Paediatr 2016;105:1487-92.  Back to cited text no. 8
Joffe MD, Alpern ER. Occult pneumococcal bacteremia: A review. Pediatr Emerg Care 2010;26:448-54.  Back to cited text no. 9
Morioka H, Iguchi M, Oodate M, Yoneda M, Ushijima F, Hirabayashi A, et al. Pneumococcal biliary tract infections – How rare are they? J Infect Chemother 2017;23:415-8.  Back to cited text no. 10
Tain YL, Lin G, Cher TW. Microbiological spectrum of septicemia and peritonitis in nephrotic children. Pediatr Nephrol 1999;13:835-7.  Back to cited text no. 11
McCashland TM, Preheim LC, Gentry MJ. Pneumococcal vaccine response in cirrhosis and liver transplantation. J Infect Dis 2000;181:757-60.  Back to cited text no. 12
Eddy AA, Symons JM. Nephrotic syndrome in childhood. Lancet 2003;362:629-39.  Back to cited text no. 13
Berical AC, Harris D, Dela Cruz CS, Possick JD. Pneumococcal vaccination strategies. An update and perspective. Ann Am Thorac Soc 2016;13:933-44.  Back to cited text no. 14
Davis TR, Evans HR, Murtas J, Weisman A, Francis JL, Khan A, et al. Utility of blood cultures in children admitted to hospital with community-acquired pneumonia. J Paediatr Child Health 2017;53:232-6.  Back to cited text no. 15


  [Figure 1]

  [Table 1]


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