Methicillin-resistant Staphylococcus aureus (MRSA) is a common multidrug resistant pathogen worldwide [1]. Emergence of community-associated MRSA (CA-MRSA) infections has a fundamentally different epidemiology compared to that of hospital-associated MRSA (HA-MRSA) infections [2]. CA-MRSA infections often do not have previous health care exposure and commonly manifests as skin and soft-tissue infections [3]. There is a paucity of data on childhood MRSA infection in developing countries. Knowledge on its prevalence and risk factors may help to plan the preventive strategies.

This study was done in the Department of Pediatrics and Microbiology, JIPMER, Pondicherry, India (August 2011 to July 2013) after obtaining clearance from the Institute Ethics Committee.

The primary objective was to identify clinical variables that could differentiate MRSA and MSSA (Methicillin-sensitive Staphylococcus aureus) infection in children (0-12 years) treated with confirmed Staphylococcus infections. Isolates were identified as S.aureus using standard microbiological methodology from blood, pus, urine, CSF (cerebrospinal fluid) and pleural fluid. Oxacillin screen agar was used to detect methicillin resistance in Mueller Hinton Agar supple-mented with 6 µg/mL of Oxacillin sodium and 4% NaCl as per Clinical and Laboratory Standards Institute recommendations [4]. Control strains used in this study were ATCC 29213 for MSSA and ATCC 43300 for MRSA.

Informed consent was taken from the parents. Baseline demographic data was recorded. Details of prior hospitalization and antibiotic usage within 12 months, history of exanthematous illness like measles and varicella, abrasion/laceration, contact with potential S.aureus carrier, malnutrition, and immunosuppressant usage were recorded. Specimens were collected at admission from all the patients except from those with hospital-acquired S.aureus infection. Children with confirmed S.aureus infection were classified into MSSA and MRSA subgroups. Cases with a previous history of hospitalization, septic shock, tricuspid valve endocarditis and pyogenic arthritis were suspected to have MRSA infection. MRSA was further classified into CA-MRSA and HA-MRSA subgroups. All the cases were followed up till discharge or death.

A case was classified as Hospital-onset if the MRSA culture was obtained on or after the fourth calendar day of hospitalization, where admission is hospital day 1; as healthcare-associated community-onset (HACO) if the culture was obtained in an outpatient setting or before the fourth calendar day of hospitalization and had one of more of the following: (i) a history of hospitalization, surgery, dialysis, or residence in a long term care facility in the previous year, or (ii) the presence of a central vascular catheter within 2 days prior to MRSA culture; and as Community-associated (CA), if none of the previously mentioned criteria were met [4].

Anemia was defined as reduction of the hemoglobin concentration below the range for age and sex [6]. Leukocytosis was defined as white blood cell (WBC) count >2 SD above the mean for age [7], and thrombocytopenia as platelet count <1,50,000/cu mm [8]. Sepsis: Systemic Inflammatory Response Syndrome (SIRS) associated with suspected or proven infection (by positive culture, tissue stain, or polymerase chain reaction test) as per International Pediatric Sepsis consensus conference guidelines [7].

Out of 210 patients screened, 98 isolates were S.aureus. Out of 98 isolates of S.aureus, 52 (53%) were MSSA. Thirty seven (80%) isolates of MRSA were community acquired and 9 (20%) were hospital acquired. MRSA occurrence among skin and soft tissue infections (SSTI), empyema, and bacteremia were 44%, 66%, 30%, respectively. Demographic variables were comparable in both the groups. Associated risk factors for possible S.aureus infection could be identified in 49% of the study population (Table I). There was no significant difference in the number of children with PEM between MRSA and MSSA subgroup.

 TABLE I  Comparison of Risk Factors in Age Group of > 1 Month* – 12 Years

Proportion of cases with leukocytosis were significantly higher in the MRSA than MSSA (P< 0.03) (Table II). Susceptibility of MRSA to vancomycin was 100% and to clindamycin was 63%. Eight strains of MRSA and six strains of MSSA had inducible clindamycin resistance detected by D test. Clindamycin resistance in SSTIs was 25%. Cases with MRSA infection stayed 4.8 days longer in hospital than the MSSA. Case fatality was similar in both the groups (MRSA= 7%, MSSA= 4%; P=0.883).

TABLE II	Comparison of Laboratory Values and Clinical Course During Hospital Stay

SSTI were the predominant sites for both MRSA (42%) and MSSA (46%) followed by blood stream infection, similar to another study from India [9]. Clinical variables were not different between MRSA and MSSA subgroups. None of the clinical variables could predict MRSA infection at admission like other studies [10,11].

Though nearly half of the cases with MSSA had leukocytosis, significant leucocytosis was most often associated with MRSA infection. Presence of leukocytosis in staphylococcal bone and joint infections was an excellent predictor of MRSA in two other studies [12,13].

Following an uniform antibiotic policy of administering cloxacillin to all the suspected staphylococcal infection, antibiotic change to vancomycin was needed in 67% of cases who later grew MRSA. Among very sick children treated with vancomycin for suspected MRSA, switching over to cloxacillin was needed in 23% as they grew MSSA. Hence, severity of clinical condition at admission may not be a useful indicator to initiate empiric antibiotic therapy for MRSA.

Convenience sampling was used in this study. Culture isolation was performed at a single tertiary center; therefore, the findings may not be extrapolated to other areas where circulating strain types may differ. Multicentric studies with a larger population involving community may be needed to validate these findings. Differentiation between CA-MRSA and HA-MRSA was based on epidemiological factors alone and not on molecular analysis of SCC mecs, which is the gold standard.

Risk factors being similar in MRSA and MSSA infections, standard hygienic measures and proper treatment guidelines would be beneficial in controlling both MRSA and MSSA. Empiric antibiotics for suspected staphylococcal infection must be guided by frequently analyzing the hospital culture isolates and sensitivity pattern rather than relying on clinical variables and pointers in the history.

Contributors: KS and NB: were involved in designing the study and management of the patients; KS: collected the data and reviewed the literature. NB conceptualized the study, reviewed the literature and critically reviewed the manuscript; SS: provided guidance regarding laboratory evaluation and also critically reviewed the manuscript. All authors contributed to drafting of the manuscript and approved the final version of the manuscript.

Funding: None; Competing interest: None stated.