Nasal Carriage and Antimicrobial Susceptibility of Staphylococcus aureusin healthy preschool children in Ujjain, India

Staphylococcus aureus is a common pathogen responsible for community as well as hospital-associated infections. The infections caused by S. aureus have clinical range from minor skin infections to severe life threatening infections [1]. There is increasing evidence that community acquired methicillin-resistant S. aureus (CA-MRSA) is spreading among healthy individuals, especially children [2].

The anterior nares have been shown to be the main reservoir of S. aureus in both adults and children. The S. aureus is transmitted to nares by contaminated hands and from surfaces where it can survive for months [3]. Nasal carriage of S. aureus acts as endogenous reservoir for clinical infections in the colonized individual but also as a source of cross-colonization for community spread. The spread of colonization occur especially in close contact areas like schools, pre-schools or households [2] probably by the contaminated hands and surfaces.

The individuals colonized with S. aureus (both CA-MRSA and CA-MSSA ie, community acquired methicillin-sensitive S. aureus) tend to have a complicated clinical course from a disease originating from their endogenous S. aureus [3]. The complicated clinical course results from increasing resistance in S. aureus isolates and also because the bacteria can cause deep-seated infections and sepsis [3, 4]. The difficulties in treating these deep-seated infections and sepsis require urgent measures to prevent further spread of MRSA. Setting up a bacterial surveillance system is one of the strategies to understand the epidemiology of MRSA to guide local antibiotic policy and to compare resistance patterns with other international surveillance systems. An improved understanding of epidemiology and resistance mechanisms of community acquired MRSA is required for designing better preventive strategies for further spread of resistance.

In India studies have been done in adults in intensive care units [5–8] and among patients at high risk of S. aureus infection [9] but studies on prevalence of nasal carriage and antibiotic susceptibility pattern of S. aureus in Indian children are few [10, 11]. Further, prevalence studies in India have been done in children aged between 5 to 15 years of age but little is known about epidemiology of S. aureus in children below five years of age. Ramana et al [10] studied 392 children, aged 5 to 15 years and showed a carriage rate of 16% for S. aureus of which 19% were MRSA. Other Indian study by Chatterjee et al [11] using polymerase chain reaction (PCR) studied 489 children, aged 5 to 15 years and showed a prevalence of 52.5% for S. aureus of which 3.8% were MRSA.

The present study is done to understand the epidemiology of nasal carriage of S. aureus in view of paucity of studies in healthy children below five years of age in India. The first objective of the study was to estimate the prevalence of nasal carriage of S. aureus and MRSA as well as to identify factors associated with such carriage among healthy children (below 5 years of age). The second objective was to study the sensitivity patterns of the isolates.

This was a prospective study conducted during 15 months from November 2007 to February 2009.

This is the first study from India reporting S. aureus nasal carriage rate in healthy children below 5 years. The study showed that 6.3% of healthy children below 5 years attending outpatient clinics of two hospitals in Ujjain carried S. aureus out of which 16.3% were MRSA. Ramana KV et al [10] reported a prevalence of 16% for S. aureus, 19% of which were MRSA among school going children (5 to 15 years) in Narketpally, Andhra Pradesh, India. However, the factors associated with acquisition of S. aureus where not evaluated in that study. In another study of 489 school children (5 to 15 years of age) by Chatterjee SS et al [11] using enriched culture media and PCR assay for mecA gene, colonization was found in 256 (52.5%) children. Out of these 3.9% were MRSA. They identified living in mud-thatch housing as factor associated with nasal carriage in their study.

The prevalence of colonization with S. aureus has previously been shown to be age dependent [2–4, 16–18]. The prevalence varied across different age groups in our study with lower prevalence in the first six months of life although these differences were not statistically significant. The peak of colonization with a respiratory pathogen may be seen at 2-3 years of age [18]. During this age a lot of pathogens compete for colonization of the anterior nares; examples are pneumoccoci, Haemophilus influenzae, Moraxella catarrhalis and S. aureus. Bacterial interference, phenomenon by which colonization by one bacterial strain prevents colonization by another strain, plays an important role in establishing or eliminating one bacterial strain over another [15].

In our study the children attending school or anganwadi (Government of India run mother and child (0 to 6 years) services) were shown to have significantly higher prevalence of carriage. The finding is consistent with the fact that large family size with 10 or more members had higher carriage prevalence as compaired to families with less than or equal to 4 members. This might be due to poor hygiene and overcrowding. Recent studies have demonstrated the importance of close contacts within households [19] and with parents [20] in spread of S. aureus carriage among children residing in the same household. In the above two studies the children shared the genotype of S. aureus with one of the parents, more often the mother indicating the importance of close contact within the family.

Hospitalization in the recent past was not a factor significantly associated with nasal carriage in our study. However, hospitalization has been demonstrated by other studies [3, 16, 21–23] as a significant risk factor. Similarly, hospital visit is considered a risk factor [3] for acquiring S. aureus carriage however; in our study hospital visit was not identified as a statistically significant factor associated with nasal carriage.

In our study we did not find exposure to antibiotics in the past 2 weeks as an important factor associated with S. aureus carriage. However, in our study too, two of the four children carrying MDR isolate of MSSA and one of the three children carrying MDR MRSA isolates had reported history of hospitalization. Many of these children had received antibiotics in the last two weeks.

A meta-analysis by Costelloe et al [24] discussed the effect of antibiotic exposure on resistance over 12 months in MRSA isolated from skin abrasions. The authors reported a pooled OR of 1.04 with confidence interval crossing the null. But, the meta-analysis had only three studies included in it. Also, as in the present study, data on antibiotic exposure was by parental reports only, which was the case in two of the three studies included in the meta-analysis [24]. Antibiotic use is one of the most important determinants of antibiotic resistance [24]. A high antibiotic use rate is reflected by the fact that 26% of children enrolled in the study had received an antibiotic in the previous two weeks. Antibiotic stewardship programmes that promote judicious use of antibiotic are urgently needed and could prove to be more cost effective then targeted screening based on risk factors, isolation of the carriers and decolonization [24]. Simple hygiene measures like hand washing are effective in preventing spread of resistant organisms in the community. The importance of hygiene is exemplified in an intervention program in Swedish day care centres, which introduced alcohol-based hand washing for children. This intervention significantly reduced (by 12% points) children's absence from the day care [25].

Early in the global epidemic of MRSA there was a clear distinction in susceptibility pattern of CA-MRSA and hospital associated MRSA (HA-MRSA), with CA-MRSA being susceptible to most antibiotics and typically highly sensitive to clindamycin [26]. Recent studies, however, demonstrate that the boundaries between these two entities are getting blurred [21, 23, 26]. This may be due to simultaneous horizontal transmission of multiple HA-MRSA strains in the community; indicating established transmission of HA-MRSA in the community for some time [27]. The S. aureus isolates in our study show high sensitivity to clindamycin but have high resistance to co-amoxiclav. This may represents a scenario of a late stage of spread in the community, albeit at a low rate [26, 27].

In MRSA isolates resistance was seen to antibiotics that are important for empirically treating severe infections. These antibiotics include doxycycline (44%), levofloxacin (31%) and clindamycin (5%). Resistance to levofloxacin and clindamycin is a cause of concern because of their therapeutic value in treating serious S. aureus infections in high-risk patients. However, it is important to note that the present results are of carriage state and not clinical infections.

Our study has limitations; firstly, we did not use an enriched media for culture of S. aureus, which might have reduced our detection rates. Secondly, we did not measure the minimum inhibitory concentration (MIC), which is the recommended method especially for glycopeptide antibiotics. However, we did not notice resistance to gycopeptides in our study. Also, we did not do confirm MRSA status by doing mecA gene due to financial constrains. Thirdly, our study is an observational study conducted in hospital setting although with healthy children from the community. A community based cohort design with sampling of a given child at various ages would have identified persistent carriage (carriage over time), which is more important source for community spread.

This is the first study among Indian children below five years of age studying the prevalence of nasal carriage and showed a prevalence of 6.3% for S. aureus 16.3% of which were MRSA. The study shows that attending pre-school or school and living in a large family was associated with nasal carriage of S. aureus. More studies with cohort design are needed to accurately assess the epidemiology of S. aureus nasal carriage in various geographical locations.