Disseminated Staphylococcal Disease in Neonates Admitted to Pediatric Emergency of a Developing Economy: Clinicomicrobiological Profile, Management, and Outcome

INTRODUCTION

Staphylococcus aureus is a well-known pathogen causing a wide spectrum of infections in children and adults in tropics and subtropics, ranging from minor skin infections to fatal systemic and disseminated disease.¹ The varied presentation of staphylococcal infection and disseminated staphylococcal disease in pediatric population has been highlighted in several studies.^2–6 The management of disseminated staphylococcal disease consist of prompt diagnosis, timely and appropriate antibiotics, prompt surgical drainage of collections, cardiorespiratory monitoring, and supportive care.^5,6 The reported mortality in children with staphylococcal bacteremia ranges from 1.4% to 30–35%.^1,2,7 A decade ago, experience about the clinical and microbial profile, critical care needs, management, and outcome of children admitted to pediatric intensive care unit with diagnosis of disseminated staphylococcal disease from our center was published.^5,6

Neonates are predisposed to staphylococcal infection, and risk factors include prematurity, low birth weight, prolonged hospitalization, and presence of invasive devices.⁸ However, data about disseminated staphylococcal diseases in neonates are scanty. Therefore, we conducted this retrospective study over a period of 1 year to review the demographic, clinical, and microbial features; management issues; and short-term outcome of neonates with disseminated staphylococcal disease.

MATERIALS AND METHODS

This retrospective study was conducted in neonatal unit for outborn neonates in pediatric emergency [neonatal unit in pediatric emergency (NUPE)] of a tertiary-care teaching hospital in North India over a period of 12 months (January–December 2018). Outborn neonates (%3C;28 days of postnatal age or <44 weeks corrected gestational age if born at <37 weeks) who were admitted in pediatric emergency during study period with diagnosis of disseminated staphylococcal disease were enrolled.

Admission files were retrieved from medical record department, and data were recorded on a predesigned study pro forma. The data regarding demographic variables such as age, sex, gestation, birth weight, mode of delivery, and perinatal details were recorded. Details regarding current illness including presenting complaints, duration of illness, treatment details in referring hospital, and risk factors for disease were recorded. Disease localization, laboratory parameters, microbiological details, complications related to disease, treatment details (antibiotics, surgical interventions, vasoactive drugs, and mechanical ventilation), duration of hospital stay, and final outcome (survived or death) were also noted.

Disseminated staphylococcal disease was defined as pyogenic infection of two anatomically noncontiguous organs and/or culture of Staphylococcus aureus or demonstration of clustered gram-positive cocci from at least one normally sterile body fluid.^5,6 Acute kidney injury (AKI) was defined as per KDIGO guidelines.⁹ Septic shock was defined by the presence of impaired perfusion requiring crystalloid bolus or inotropic support.¹⁰ Disseminated intravascular coagulation was defined by the presence of thrombocytopenia and coagulopathy (INR %3E; 1.5 or aPTT > 35 seconds).¹¹ Anemia was defined as hemoglobin <11 g/dL, leukocytosis as total leukocytic count >15,000/cumm, and thrombocytopenia as platelet count <150,000/cumm.¹²

NUPE has 20 beds with 8 to 12 admissions per day. The unit caters to outborn neonates who were referred to us from various hospitals in and around Chandigarh. At any time, there are 40 to 50 outborn neonates admitted in the unit (2–3 neonates on a single cot). In each shift, there are four to five junior residents, one to three senior residents, one to two consultants, and three staff nurses managing the unit. There are facilities for oxygen and CPAP administration, monitoring by pulse oximetry, infusion pumps, phototherapy, orogastric feeding, double volume exchange transfusion, and ROP screening. Recently, the unit is equipped with eight ventilators (for noninvasive and invasive ventilation). The unit has radiodiagnosis, pediatric surgery, pediatric cardiology, cardiothoracic surgery, ophthalmology, laboratory back-up, and blood bank services. Neonates are being referred from government and private hospitals in Chandigarh, Punjab, Haryana, Himachal Pradesh, Jammu and Kashmir, and Uttar Pradesh. Once stabilized, these neonates are either discharged or back referred to the referring unit or nearby sick newborn care units. After discharge, neonates are followed in pediatric outpatient department in our center.

RESULTS

DISCUSSION

We reported 26 neonates with disseminated staphylococcal disease. Skin and subcutaneous abscesses were the commonest localization of infection followed by pneumonia, meningitis, osteomyelitis, and septic arthritis. Predisposing conditions were seen in less than half of cases. Staphylococcus was isolated in 53.8% cases and MRSA accounting for 71.4% of isolates. Respiratory failure, shock, and AKI were noted in one-third of cases. The duration of intravenous antibiotics was around 2 weeks, half of the cases needed incision and drainage, one-fourth needed vasoactive drugs, and one-fifth needed mechanical ventilation. The duration of hospital stay was 21/2 weeks, and mortality was 15%. This is first study involving neonates with disseminated staphylococcal disease.

Staphylococcus aureus is a well-known pathogen in pediatric as well as neonatal population to cause skin and subcutaneous abscesses, blood stream infections, and other deep-seated abscesses. Disseminated staphylococcal disease is reported in children associated with high mortality and morbidity. In the preantibiotic era, it was as high as 80%, which has decreased to about 20%.^13,14 The literature on neonatal disseminated staphylococcal disease is scarce. Risk factors for staphylococcal disease include trauma, immunocompromised status, presence on invasive devices, and chronic medical illness.¹⁵

Other interesting findings of this study are as follows: most of the cases were term born and presented after first week of life with %3E;50% in fourth week of life. Since our hospital is a tertiary-care teaching institute, over 80% of cases had prior hospital stay and similar number received parenteral antibiotics prior to referral. Anemia was also quite prevalent, affecting nearly three-fourth of cases and could be due to nutritional cause, sampling losses, or as a part of illness. Thrombocytopenia was seen in 40% of cases. Half of the cases had hyponatremia, probably secondary to syndrome of inappropriate antidiuretic hormone secretion (SIADH). AKI was seen in 27% cases and was nonoliguric and none required renal replacement therapy. All these complications became passive at time of discharge.

Drug resistance is a major problem with Staphylococcus aureus.¹⁶ Prevalence of MRSA is highly variable from 17 to 56%, while that of VRSA is <14%.^17–19 We noted a high prevalence of MRSA (71.4%) probably due to the fact that majority of cases were referred to us from different hospitals and had majority had received antibiotics for more than a week. These isolates could be hospital acquired. We were not able to isolate organism in about half of the cases probably due to the fact that majority of the cases had received parenteral antibiotics prior to referral. The recent reports of rising MRSA in community is worrisome issue.²⁰

The treatment of disseminated staphylococcal disease include early initiation of appropriate antibiotics per local sensitivity patter after collection of appropriate samples for culture, removal of foci of infection, and aggressive source control.^5,6 Predictors of morbidity and mortality include positive blood cultures persisting for >48 hours, persistent fever, implanted device, skin lesions, immunosuppression, and multiorgan involvement.²⁰ In index study, appropriate antibiotics were used for about 2 weeks, half required incision and drainage of abscesses, and 20% needed arthrotomy. The overall outcome was good, with 85% survival rate. We did not note any pleural or pericardial suppurative complications. In contrast, Baranwal et al.^5,6 noted that in children with disseminated staphylococcal disease (n = 53), the pleuropulmonary disease was there in 89% and pericardial effusion in 40%.

Hieber et al.² reported 15 children with disseminated staphylococcal disease and 13 had cutaneous manifestations. Authors noted that an absolute neutrophil count >10,000/cumm and band forms >500/cu mm were predictors of disseminated disease and the mortality was 27%. Kabra et al.³ reported 10 children with disseminated staphylococcal disease. The involved organs include skin and respiratory system in 80%, liver in 70%, and pericardial effusion in 50%. MSSA was the commonest isolate (80%). The average duration of hospital stay was 32 days and mortality 20%. There were no identifiable predisposing factors and no predictors of mortality were identified. Half of the cases had history of minor trauma. Common systems involved were musculoskeletal system followed by respiratory system. Organism could be isolated in 78%, and of them 12% were MRSA. Median hospital stay was 15 days, and mortality rate was 8.6%. Mandal et al.²¹ noted that in 36 children with disseminated staphylococcal disease, blunt trauma was the commonest precipitating factor, all isolates were MRSA, and 89% demonstrated vancomycin resistance. From our institute, Baranwal et al.^5,6 reported 53 children with disseminated staphylococcal disease. Fever and respiratory distress were the commonest presentation. Pleuropulmonary and pericardial involvement was much higher (89% and 40%, respectively), whereas we did not notice any pleural or pericardial involvement. MSSA accounted for 91% of isolates (40 of 44 isolates), whereas we noticed increased prevalence of MRSA (70%). Complications were much more prevalent in their cohort when compared to index study (shock 90% vs 27%, need for invasive ventilation 32% vs 19%). The mortality is 13.2% (10/53) as in our study (15%, 4/26). Presence of both septic shock and need for mechanical ventilation were associated with high mortality (RR, 20.5; p < 0.001), similar to index study.

The strengths of this study are that this is the first study to document clinicomicrobiological profile, complications, management, and outcome of neonates with disseminated staphylococcal disease. The limitations include retrospective nature of the study. The data on long-term follow-up of these cases is not available. The information whether the organisms were community acquired or hospital acquired is not available. We assumed that majority were hospital acquired, as majority of the cases came to us from other hospitals.

CONCLUSION

Disseminated staphylococcal disease is an underreported disease in neonates. When compared to the pediatric population, complication rates were less, but mortality seems to be similar. MRSA is the predominantly isolated pathogen. High index of suspicion, early diagnosis, prompt appropriate antibiotics, and early surgical debridement are integral part of management.

REFERENCES

1. Ladhani S, Konana OS, Mwarumba S, et al. Bacteremia due to Staphylococcus aureus. Arch Dis Child 2004;89(6):568–571. DOI: 10.1136/adc.2003.026781.

2. Hieber JP, Nelson AJ, McCracken GH.Jr Acute disseminated staphylococcal disease in childhood. Am J Dis Child 1977;131(2):181–185. DOI: 10.1001/archpedi.1977.02120150063012.

3. Kabra SK, Jain Y, Kataria A, et al. Disseminated staphylococcal disease. Indian Pediatr 1996;33(8):683–685.

4. Miles F, Voss L, Segedin E, et al. Review of Staphylococcus aureus infections requiring admission to a paediatric intensive care unit. Arch Dis Child 2005;90(12):1274–1278. DOI: 10.1136/adc.2005.074229.

5. Baranwal AK, Singhi SC, Jayashree M. A 5-year PICU experience of disseminated staphylococcal disease, part 1: clinical and microbial profile. J Trop Pediatr 2007;53(4):245–251. DOI: 10.1093/tropej/fmm022.

6. Baranwal AK, Singhi SC, Jayashree M. A 5-year PICU experience of disseminated staphylococcal disease, part 2: management, critical care needs and outcome. J Trop Paediatr 2007;53(4):252–258. DOI: 10.1093/tropej/fmm023.

7. Suryati BA, Watson M. Staphylococcus aureus bacteraemia in children: a 5-year retrospective review. J Paediatr Child Health 2002;38(3):290–294. DOI: 10.1046/j.1440-1754.2002.00787.x.

8. Fortunov RM, Hulten KG, Hammerman WA, et al. Community-acquired Staphylococcus aureus infections in term and near-term previously healthy neonates. Pediatrics 2006;118(3):874–881. DOI: 10.1542/peds.2006-0884.

9. Khwaja A. KDIGO clinical practice guidelines for acute kidney injury. Nephron Clin Pract 2012;120(4):c179–c184. DOI: 10.1159/000339789.

10. Singer M, Deutschman CS, Seymour CW, et al. The third international consensus definitions for sepsis and septic shock (Sepsis-3). JAMA 2016;315(8):801–810. DOI: 10.1001/jama.2016.0287.

11. Venugopal A. Disseminated intravascular coagulation. Indian J Anaesth 2014;58(5):603–608. DOI: 10.4103/0019-5049.144666.

12. Goyette RE, Key NS, Ely EW. Hematologic changes in sepsis and their therapeutic implications. Semin Respir Crit Care Med 2004;25(6):645–659. DOI: 10.1055/s-2004-860979.

13. MacNeal WJ, Frisbee FC. One hundred patients with Staphyloccocus septicemia receiving bacteriophage service. Am. J. Med. Sci 1936;191:179–189. DOI: 10.1097/00000441-193602000-00004.

14. Benfield T, Espersen F, Frimodt-Møller N, et al. Increasing incidence but decreasing in-hospital mortality of adult Staphylococcus aureus bacteraemia between 1981 and 2000. Clin Microbiol Infect 2007;13(3):257–263. DOI: 10.1111/j.1469-0691.2006.01589.x.

15. Laupland KB, Ross T, Gregson DB. Staphylococcus aureus bloodstream infections: risk factors, outcomes, and the influence of methicillin resistance in Calgary, Canada, 2000-2006. J Infect Dis 2008;198(3):336–343. DOI: 10.1086/589717.

16. Khan MF. Brief history of Staphylococcus aureus: A focus to antibiotic resistance. EC Microbiol 2017;5(2):36–39.

17. Hassoun A, Linden PK, Friedman B. Incidence, prevalence, and management of MRSA bacteremia across patient populations-a review of recent developments in MRSA management and treatment. Crit Care 2017;21(1):211. DOI: 10.1186/s13054-017-1801-3.

18. El Sayed N, Ashour M, Amine AEK. Vancomycin resistance among Staphylococcus aureus isolates in a rural setting, Egypt. Germs 2018;8(3):134–139. DOI: 10.18683/germs.2018.1140.

19. Deurenberg RH, Stobberingh EE. The evolution of Staphylococcus aureus. Infection, genetics and evolution 2008;8(6):747–763. DOI: 10.1016/j.meegid.2008.07.007.

20. Tong SY, Davis JS, Eichenberger E, et al. Staphylococcus aureus infections: epidemiology, pathophysiology, clinical manifestations, and management. Clin Microbiol Rev 2015;28(3):603–661. DOI: 10.1128/CMR.00134-14.

21. Mandal K, Roy A, Sen S, et al. Disseminated staphylococcal disease in healthy children-experience from two tertiary care hospitals of West Bengal. Indian J Pediatr 2014;81(2):133–137. DOI: 10.1007/s12098-013-1034-7.