Microbiological profile and role of streptokinase in empyema thoraces in children – A retrospective and observational study from a tertiary care teaching hospital from North Karnataka

INTRODUCTION

Empema thoracis in children causes significant morbidity and mortality. It was estimated that 0.6% of childhood pneumonia progress to empyema.^[1,2] Empyema thoraces constitutes approximately 5–10% of cases seen by paediatricians in India.^[3] Empyema continues to have mortality rate of 5–7%.^[4]

Pattern of organisms in the pleural fluid has been varying. Most common causative organisms of empyema are Streptococcus pneumoniae, Staphylococcus aureus, Escherichia coli, Haemophilus influenza, Klebsiella pneumonia, Streptococcus pyogenes and uncommon causative organisms are Mycobacterium tuberculosis and Cryptococcus neoformans.^[5,6] In last five decades in developed countries the microbial profile has changed.^[7] The prevalence of S. aureus rose and the development of Staphylococcal resistance was observed, but the scenario in developing countries is very different. Even with the use of broad-spectrum antibiotics, prevalence remains high.

Optimal management in children is not clear; however, the mainstay of treatment as per British Thoracic Society (BTS) guidelines is systemic antibiotics and chest tube drainage the role of fibrinolytic agents not yet clear.

Use of streptokinase, urokinase and alteplase has resulted in significant resolution of empyema, with decreased morbidity as well as surgical intervention.^[8-10] Contrast to this, some studies have been unable to demonstrate any benefit of intrapleural fibrinolytic therapy in the treatment of empyema in children.^[11] Hence, the role of streptokinase is not clear. We present 2-year experience (2017–19) from a tertiary care centre from North Karnataka to provide evidence for the need to optimise the existing management guidelines.

MATERIAL AND METHODS

This was a retrospective study, conducted at Department of Paediatrics, KIMS, Hubli from Jan 2017 to Dec 2019.

RESULTS

Total of 33 children fulfilled the inclusion criteria. [Figure 1] shows the flow chart of study children.

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Figure 1:

Flow chart of study

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[Table 1] shows baseline characteristics of study children. Mean age was 5.25 ± 1.14 years with Male to female ratio of 1.2:1. Most common age group was 1–5 years (39.39%), of them 54.54% were males and 57.57% belonged to Class III Socio-Econamic Status (SES). The predisposing factors for empyema were severe acute malnutrition (05), nephrotic syndrome (01) and congenital heart disease (01).

Clinical manifestations at presentation of frequency were fever 100% (33), cough 87.8% (29), dyspnoea 78.78% (26), intercostal bulging 36.36% (12), pallor (65%), cyanosis (25%) and pedal oedema (10%).

In the present study, 42.5% had involvement of the right zone of chest, Chest X-ray revealed, along with effusion, 29.5% had consolidation, 20.5% had collapse and 2% had hydropneumothorax.

Mean haemoglobin was 9.54 ± 1.84 g%, mean total leukocyte count was 18055.75 ± 27996.66.67.5%. CRP was positive in 27 (67.5%) children.

In 11 children, organisms were isolated in pleural effusion. Among them, 54.54% (06) were S. aureus, 18.18% (02) S. pneumonia, 9.09% (01) non-fermenting Gram-negative Bacilli, 9.09% (01) Pseudomonas and 9.09% (01) Citrobacter koseri. Only one child (2.5%) had non-fermenting Gram-negative Bacilli grown o blood culture.

[Table 2] shows organisms along with antibiotic sensitivity pattern. S. aureus was sensitive to vancomycin and linazolide while S. pneumonia was sensitive to ceftriaxone. All children were treated initially with third generation cephalosporins and later antibiotics were changed as per antibiotic sensitivity reports. Intercostal drainage was performed in all children of empyema thoraces. Only one child required surgical therapy (decortication). Transthoracic USG was performed in all children. Fourteen children showed septations on USG chest. All fourteen children received streptokinase.

[Table 3] shows the effect of streptokinase in terms of duration and outcome. Among those subjects who received streptokinase, 100% were discharged (improved). Children who did not receive streptokinase had 11.5% mortality. There was no statistical significant association between outcome (mortality) and streptokinase. Mean duration of hospital stay among those who received streptokinase was 13.79 ± 4.51 and who did not receive was 14.73 ± 8.26 days. There was no significant difference in the mean duration of hospital stay with respect to streptokinase usage.

DISCUSSION

An increasing incidence of parapneumonic effusion and pleural empyema has been reported in developing countries in recent studies.^[15] Paediatric age group is an important risk factor for invasive pneumococcal diseases, with incidence being highest in young children.^[16,17] In our study, 1.07% of childhood pneumonia had synpneumonic effusion and 0.88% progressed to empyema.

The bacteriology of pleural infection has been changing in recent years since the introduction of antibiotics in the 1940s.^[7] In the present study, among the organisms isolated, most common was S. aureus (54.54%) followed by S. pneumonia (18.18%). S. aureus was the most common organism detected on pleural fluid culture in the study conducted by Lingayat and Wankhade^[12] and Ramireddy and Krishna^[6] which is similar to our study. Likewise, in a study by Baranwal et al.,^[16] S. aureus was the most common organism isolated from pleural fluid (77%). This is related to the emergence of worldwide spread of methicillin-resistant and methicillin susceptible strains. The virulence of S. aureus is due to surface adhesins, toxins, enzymes and superantigens. Panton-Valentine leucocidin is a distinctive virulence factor associated with highly aggressive and fatal form of infection.^[18] In a study conducted by Stankey et al.,^[19] pleural fluid isolates were S. pneumoniae (48%) followed by group A Streptococcus (27%). S. pneumoniae is an extracellular pathogen characterised by a thick polysaccharide capsule. Specific splenic functions required for immunoglobulin responses to polysaccharide antigens were lacking in children under 2 years. They cannot effectively combat capsulate bacteria and struggle to control pneumococcal colonisation of the nasopharynx, mucosal infections (such as otitis media, sinusitis and pneumonia) and invasive infections (bacteraemia and meningitis).^[20]

In our study, 14 children received intrapleural streptokinase. All those children who received streptokinase were improved and discharged. We also observed, there was a decreased duration of hospital stay in streptokinase group, but this was not statistically significant. No adverse effect of streptokinase was noted. Study by Aydoğan et al.,^[21] there were no significant differences in terms of clinical outcomes between the two groups. The average length of hospital stay was 19.1 ± 5.5 and 21.9 ± 11.2 days for the drainage and streptokinase groups, respectively. In another study by Altmann et al.,^[22] they found no evidence of difference in overall mortality with fibrinolytic versus placebo (Odds ratio 1.16, 95% Confidence interval 0.71–1.91, I² = 0%) whereas in the study by Ekingen et al.,^[23] there was statistically significant difference between two groups according to date of admission (6.8 vs. 10.4 days) and total length of hospital stay (16.6 vs. 22.4 days). Similarly, use of fibrinolytic agents in paediatric empyema resulted in reduced hospital stay, increased chest tube drainage and decrease in intensity of fever in other studies.^[24,25] The decreased duration of hospital stay in our cases probably due to streptokinase usage in early stage of disease. In early stage, Streptokinase works by dissolving fibrinous clots and membranes, and prevents fluid sequestration and hence improves drainage.

The strength of our study was having good medical records; however, our study was limited by (i) as it was a retrospective study, (ii) small sample size and (iii) Children who received antibiotics prior to admission were considered that might have hampered culture growth.

CONCLUSION

Paediatric empyema is an important cause of childhood morbidity and mortality. Spectrum of organisms causing empyema is varying in recent years with S. aureus being the most common. Although use of streptokinase showed better outcome and decreased duration of hospital stay, this was not statistically significant.