|Year : 2018 | Volume
| Issue : 2 | Page : 33-37
Clinical spectrum and resistance pattern of community-acquired invasive Staphylococcus aureus infection in children
Mohd Kashif1, Yusuf Imran Ansari1, Tarique Ekram1, Fatima Khan2, Tabassum Nawab3, Shaad Abqari1
1 Department of Pediatrics, J. N. Medical College, Aligarh Muslim University, Aligarh, Uttar Pradesh, India
2 Department of Microbiology, J. N. Medical College, Aligarh Muslim University, Aligarh, Uttar Pradesh, India
3 Department of Community Medicine, J. N. Medical College, Aligarh Muslim University, Aligarh, Uttar Pradesh, India
|Date of Web Publication||10-Jan-2019|
Dr. Shaad Abqari
Department of Pediatrics, J. N. Medical College Hospital, AMU, Aligarh, Uttar Pradesh
Source of Support: None, Conflict of Interest: None
Introduction: The incidence of Staphylococcal infections has been increasing over the last 20 years and MRSA infection is becoming an important cause of hospital infection among children.
Aims and Objectives: The study aimed to delineate the clinical spectrum of Staphylococcus aureus infection in children, their complications, antimicrobial resistance patterns and response to treatment.
Materials and Methods: Children with suspected community acquired invasive S. aureus infections were retrospectively identified. Fifty patients with proven S.aureus infection on culture from clinically relevant sites were included. Their symptoms, course of disease, complications, antimicrobial resistance pattern and response to treatment is described.
Results and Conclusions: Out of a total of 50 cases, S.aureus isolates from 31 (62%) cases were sensitive to oxacillin while resistance to this antibiotic was reported in 19 (38%) cases. Most common site for localisation of infection was present in lungs (40%) followed by CNS (16%), skin (8%) and bone (4%) The focality of infection and pattern of resistance were not significantly associated with outcomes.
Keywords: Antibiotic resistance, children, methicillin-resistant Staphylococcus aureus, Staphylococcus aureus, septicaemia
|How to cite this article:|
Kashif M, Ansari YI, Ekram T, Khan F, Nawab T, Abqari S. Clinical spectrum and resistance pattern of community-acquired invasive Staphylococcus aureus infection in children. J Patient Saf Infect Control 2018;6:33-7
|How to cite this URL:|
Kashif M, Ansari YI, Ekram T, Khan F, Nawab T, Abqari S. Clinical spectrum and resistance pattern of community-acquired invasive Staphylococcus aureus infection in children. J Patient Saf Infect Control [serial online] 2018 [cited 2019 Apr 23];6:33-7. Available from: http://www.jpsiconline.com/text.asp?2018/6/2/33/249841
| Introduction|| |
The diseases caused by staphylococcal species range from minor skin infections to serious systemic sepsis that can even be fatal. The incidence of staphylococcal infections has been increasing over the last 20 years. This increase has been accompanied by the emergence of drug-resistant strains of Staphylococcus aureus. When penicillin was first introduced in 1943, no resistance was reported initially. However, due to selection pressure exerted by the use of penicillin, resistance rapidly emerged to this antibiotic, and by 1960, up to 80% strains of S. aureus were penicillin resistant. Resistance to penicillin is mediated by the production of penicillinase, an enzyme which inactivates penicillins by opening up the β-lactam ring. Penicillinase-resistant penicillins (methicillin, oxacillin, cloxacillin and flucloxacillin) were developed later for the treatment of these penicillin-resistant strains of S. aureus. Within a few years of their use, resistance to methicillin was reported first from England in 1961. Methicillin-resistant S. aureus (MRSA) remained uncommon and mainly confined to hospital settings, but since the last two decades, its prevalence has risen substantially both in hospitals and now even in the community. The resistance to methicillin/oxacillin is mediated by mecA gene which is located on the staphylococcal cassette chromosome (SCC) and causes alterations in the penicillin-binding protein 2a. It confers resistance to β-lactam antibiotics. Five SCC gene types exist. Hospital-acquired MRSA (HA-MRSA) is more likely to have Subtype II and III (large molecules, more likely to also contain multidrug-resistant genes), while community-associated MRSA (CA-MRSA) has Subtype IV and V (much smaller molecules, only carry mecA gene). Therefore, HA-MRSA is generally more drug resistant than CA-MRSA.
MRSA is now emerging organism acquired from the community, and MRSA infection has been observed in previously healthy children and adults without predisposing risk factors. According to the Centers for Disease Control and Prevention, over 75,000 cases of invasive MRSA infections were encountered in the US in 2012 with an estimated incidence of 23.99/100,000 population. A study conducted at 15 tertiary care centres in India by the Indian Network for Surveillance of Antimicrobial Resistance group reported MRSA isolates out of total S. aureus detected from various specimens among outpatients, non-intensive care unit (ICU) inpatients and ICU patients as 28%, 42% and 43%, respectively, in 2008 and 27%, 49% and 47%, respectively, in 2009.
The present study focussed on the clinical spectrum of S. aureus infection in children, its complications and prevalence of MRSA.
| Methods|| |
This is a retrospective which was conducted in the paediatric ward in a tertiary care hospital. Children between 0 and 5 years having invasive Staphylococcus infection before therapy were identified by looking through the records and patients whose cultures were positive for S. aureus (blood, pus, pleural fluid, cerebrospinal fluid [CSF] and other body tissue) were included in the study. Blood culture report of all the children was also analysed as it is done in every child with suspected infection. All specimens were collected with standard aseptic technique. Primary cultures were plated on 5% sheep blood agar. S. aureus was biochemically characterised as catalase-positive, coagulase-positive, oxidase-negative Gram-positive cocci in clusters. All isolates of S. aureus were further tested for methicillin resistance using Kirby–Bauer's disc diffusion method on Mueller-Hinton agar with 24 h incubation at 35°C. The results were interpreted according to the Clinical and Laboratory Standards Institute 2012 recommendations. The data were collected from the hospital records after taking due permission from the ethical committee, and the records of 6 months duration were analysed.
A child was considered as having S. aureus septicaemia if at least one blood culture was positive for S. aureus along with clinical features, suggestive of life-threatening end-organ damage (sequential organ failure assessment score). Community-acquired S. aureus septicaemia was defined as a bloodstream infection in a previously healthy child with no previous hospitalisation, underlying disease, central venous line, or known immunodeficiency, for whom blood cultures first yielded S. aureus within 48 h after admission to the hospital. Data regarding age, sex, nutritional status, site of infection, symptom duration and associated complications were also collected. Children were monitored for response to therapy with respect to the antibiotics used.
All subjects were admitted to the paediatric ward and were treated with antibiotics. The empirical choice of antibiotic was amoxicillin-clavulanic acid which was changed to vancomycin if culture sensitivity identified a methicillin-resistant strain of S. aureus. Study subjects were also subjected to laboratory investigations, including complete blood counts, serum electrolytes, renal function test (serum creatinine and urea), liver function test, chest roentgenogram and lumbar puncture (when indicated).
| Results|| |
A total of 50 children with community-acquired invasive S. aureus infection were identified from the records. Mean age of these children was 1.9 years (95% confidence interval [CI] 1.6–2.2) with 27 out of 50 (54%) being infants, while 30 cases being males and 20 females. A total of 13 children were severely malnourished (W/H Z-score <−3 SD). At least one blood culture was positive for S. aureus in 25 patients while rest had positive cultures from other specimens. Of a total of 50 cases, S. aureus isolates from 31 (62%) cases were sensitive to oxacillin while resistance to this antibiotic was reported in 19 (38%) cases. However, the S. aureus strains isolated from blood culture samples showed a higher prevalence of resistance to oxacillin at 48% compared to strains from samples other than blood in whom the resistance was found in only 14% cases (P < 0.05). Vancomycin was the choice of antibiotic used, and no oxacillin-resistant strain was found to be resistant to this antibiotic. Most common site for localisation of infection was present in the lungs (40%) followed by central nervous system (CNS) (20%), skin (8%) and bone (4%) [Table 1]. Pyothorax was the most common presentation and S. aureus was frequently isolated from the pus; CSF showed the growth of S. aureus in 10 (20%) children who presented with features of meningitis. Among 20 (40%) patients who had pulmonary involvement, eight cases had developed a complication of pneumothorax also. Furthermore, 34% of patients had infection at multiple sites.
Duration of fever was <7 days in 56% cases and 8–21 days in 38%. In 6% of cases, fever persisted for more than 21 days. Length of hospital stay was ≤7 days in 14%, 8–14 days in 42%, 15–28 days in 30% and ≥28 days in 14%. Two children (4%) died. Mean duration of fever and length of hospital stay were similar irrespective of the antibiotic sensitivity of the organism isolated (P > 0.05).
The most common complication was acute kidney injury with 20 patients (40%), showing an abnormal serum creatinine on presentation. Liver enzymes were raised in eight patients (16%), and thrombocytopenia with or without bleeding manifestations was present in 12 patients (24%). However, there was no significant relationship between frequency of complications and sensitivity profile of the S. aureus isolates (P > 0.05).
Further relationship with strain of S. aureus and other parameters were studied. As is clear from [Table 2], MRSA infection was not significantly associated (P > 0.05) with younger age or severe degree of malnutrition, neither was it associated with prolonged hospital stay nor adverse outcome; further, there were more cases of multifocal infection in methicillin-sensitive strain.
|Table 2: Association of sensitivity of Staphylococcus aureus strain with various parameters|
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Similarly, focality (whether unifocal or multifocal) of infection was studied [Table 3] and it was found that there was no significant association between multifocal infection with younger age, severe malnutrition or delayed attainment of defervescence; similarly, MRSA strain was also not significantly associated with poorer outcome (P > 0.05).
| Discussion|| |
The incidence of S. aureus infections and septicaemia in our country remains high. Population-based data on CA-MRSA incidence, especially in children, are lacking. Young age, participation in contact sports, colonisation with MRSA and close contact with someone who had a documented MRSA infection are known risk factors for CA-MRSA infections.
The morbidity burden from S. aureus infection is quite high. In this study, 86% of children required >7 days hospitalisation with 44% requiring hospital admission for >14 days. However, the length of stay did not differ between MRSA and MSSA infections. Many studies conducted under different settings have given conflicting results on association between mortality, cost and hospital stay with MRSA infection. Some studies have found that the outcome is poorer in children having infection with MRSA,,, while other finding no significant difference, in the overall outcome and sensitivity pattern of S. aureus infection. This apparent disagreement may have been due a number of confounding factors such as comorbidities, age and severity of illness.
A meta-analysis by Salgado et al. found CA-MRSA prevalence among hospital MRSA to be 30.2% in 27 retrospective studies and 37.3% in five prospective studies. We identified a similar figure of CA-MRSA at 38%. This shows that MRSA is not localised to only hospital-acquired infection and it is even common in community-acquired pneumonia. Pulmonary involvement is a common manifestation, especially in children.
Complication rates are high in children. We documented at least one complication in 68% of cases, with acute kidney injury being the most common. Therefore, close monitoring of all patients is necessary to identify complications early and institute appropriate treatment.
There was no significant difference found in the incidence of MRSA infection with relation to age or nutrition status of the child; similarly, even focality of infection and recovery was similar in both the groups. This observation tells us that the S. aureus infection has similar affection in children, irrespective of the resistance pattern of the strain, though a large sample size is required to substantiate this observation.
Similarly, no significant association of multifocality of infection (more than one site of localisation) with young age and severe malnutrition was found. This analysis was done presuming that staphylococcal infection might be more severe in young and malnourished children. Furthermore, multifocal infection did not affect the length of stay or outcome in terms of recovery within a month time. This shows that morbidity is similar whether it affects a single organ system or multiple and is not affected with the nutritional status of the child.
This study points to alarming rise of CA-MRSA, 38% of isolates were oxacillin resistant with S. aureus strains isolated from blood culture samples showed an even higher incidence of resistance to oxacillin at 48% and this is really a point of concern as half of all infections were blood culture positive. We will soon run out of the sensitive antibiotics; though all strains were sensitive to vancomycin, it is just matter of time that we will start seeing resistance to this reserved drug also because of rampant use in hospital settings. Although we have not found any significant association between severity of infection and morbidity in terms of time of recovery with MRSA as compared to MSSA, definitely, the cost of treatment is much higher in MRSA group, especially its use in patients with septicaemia which needs a prolonged course.
Limitations of the study
The study provides an insight into the spectrum of S. aureus infection and its resistance pattern; however, other variables such as prior antibiotic use needed to be investigated and was not considered.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Chambers HF. The changing epidemiology of Staphylococcus aureus
? Emerg Infect Dis 2001;7:178-82.
Patricia JM. Celbenin - resistant Staphylococci. Br Med J 1961;1:1245.
Johnson AP, Aucken HM, Cavendish S, Ganner M, Wale MC, Warner M, et al.
Dominance of EMRSA-15 and -16 among MRSA causing nosocomial bacteraemia in the UK: Analysis of isolates from the European antimicrobial resistance surveillance system (EARSS). J Antimicrob Chemother 2001;48:143-4.
Kainthola A, Bhatt AB. Population based prevalence of community acquired methicillin resistant Staphylococcus aureus
in community settings of Srinagar Garhwal, India. Rec Res Sci Technol 2013;5:60-2.
Kaplan SL, Hulten KG, Gonzalez BE, Hammerman WA, Lamberth L, Versalovic J, et al.
Three-year surveillance of community-acquired Staphylococcus aureus
infections in children. Clin Infect Dis 2005;40:1785-91.
Joshi S, Ray P, Manchanda V, Bajaj J, Chitnis DS, Gautam V, et al
. Indian Network for Surveillance of Antimicrobial Resistance (INSAR) group, India. Methicillin resistant Staphylococcus aureus
(MRSA) in India: Prevalence & susceptibility pattern. Indian J Med Res 2013;137:363-9.
Beam JW, Buckley B. Community-acquired methicillin-resistant Staphylococcus aureus
: Prevalence and risk factors. J Athl Train 2006;41:337-40.
Kang CI, Song JH, Chung DR, Peck KR, Ko KS, Yeom JS, et al.
Clinical impact of methicillin resistance on outcome of patients with Staphylococcus aureus
infection: A stratified analysis according to underlying diseases and sites of infection in a large prospective cohort. J Infect 2010;61:299-306.
Wolkewitz M, Frank U, Philips G, Schumacher M, Davey P; BURDEN Study Group. Mortality associated with in-hospital bacteraemia caused by Staphylococcus aureus
: A multistate analysis with follow-up beyond hospital discharge. J Antimicrob Chemother 2011;66:381-6.
Rieg S, Peyerl-Hoffmann G, de With K, Theilacker C, Wagner D, Hübner J, et al.
Mortality of S. aureus
bacteremia and infectious diseases specialist consultation – A study of 521 patients in Germany. J Infect 2009;59:232-9.
Turnidge JD, Kotsanas D, Munckhof W, Roberts S, Bennett CM, Nimmo GR, et al. Staphylococcus aureus
bacteraemia: A major cause of mortality in Australia and New Zealand. Med J Aust 2009;191:368-73.
Wyllie DH, Crook DW, Peto TE. Mortality after Staphylococcus aureus
bacteraemia in two hospitals in Oxfordshire, 1997-2003: Cohort study. BMJ 2006;333:281.
Salgado CD, Farr BM, Calfee DP. Community-acquired methicillin-resistant Staphylococcus aureus
: A meta-analysis of prevalence and risk factors. Clin Infect Dis 2003;36:131-9.
Gonzalez BE, Martinez-Aguilar G, Hulten KG, Hammerman WA, Coss-Bu J, Avalos-Mishaan A, et al.
Severe staphylococcal sepsis in adolescents in the era of community-acquired methicillin-resistant Staphylococcus aureus
. Pediatrics 2005;115:642-8.
[Table 1], [Table 2], [Table 3]