Prevalence of Methicillin-resistant Staphylococcus Aureus in Saudi Arabia Revisited: A Meta-analysis

1. INTRODUCTION

Antibiotic resistance of a significant number of bacterial pathogens has emerged as a growing public health threat, attracting the attention of many health organizations, as it hinders the efforts of effectively preventing and treating the increased bacterial infections [1]. The medical and economic implications of the spread of both hospital and community-associated multidrug-resistant bacteria were reported by a number of studies [2-5].

Staphylococcus aureus is a common skin normal flora that causes less common infections following breaks in the skin or mucous membrane, ranging from superficial skin and soft tissue infections to life-threatening toxic shock syndrome, endocarditis, and sepsis [6, 7].

Historically, the introduction of penicillin as a treatment regimen for S. aureus infections was a very effective method, however, by the mid of the twentieth century, the bacteria had already developed resistance to the drug by producing beta-lactamase enzyme which inactivates penicillin, ampicillin, and amoxicillin. This necessitated the production of beta-lactamase stable antibiotics such as methicillin and cloxacillin [1]. In the early sixties of the last century, the first Methicillin-Resistant Staphylococcus Aureus (MRSA) was identified [8], initially, as a Hospital-Acquired (HA-MRSA), and later, Community-Acquired (CA- MRSA) started to emerge and dramatically increase in number in many countries [1]. Both asymptomatic and opportunistic forms of MRSA were reported in animals, though they occur transiently, they present a potential source of community-acquired infection [9]. HA-MRSA and CA-MRSA have typically different microbiological characteristics, risk factors, and clinical manifestations. For instance, the CA-MRSA causes less severe disease for the majority of the infections [10]. The MRSA resistance is highly attributed to the presence of mecA or mecC genes in the bacterial chromosome. These genes code for different versions of penicillin-binding proteins that interfere with the binding of beta-lactam antibiotics to the bacterial cell wall [9].

The prevalence of MRSA infections shows a range of 13% - 74% worldwide [11], while in Europe, it ranged from 0.9% to 56% in 2014 [12]. In the US, the Center for Disease Control and Prevention (CDC) reported an approximately 50% of S. aureus nosocomial infections in the intensive care units were caused by MRSA [13].

A considerable variation was reported in the prevalence of MRSA in the Gulf Corporation Council Countries (GCC), with Saudi Arabia showing the highest prevalence rate of 29.9%, while Kuwait showed the lowest of 3.3% [14]. Numerous studies from Saudi Arabia have also reported an increase in the prevalence rate of MRSA [15-17]. This increase in the MRSA cases was attributed to the large influx of expatriates and pilgrims from all over the world. The present study included all recently published studies, which add strength and weight to the result, considering that the only previous attempt to pool the prevalence rates of MRSA in Saudi Arabia included studies date at least decade ago. Determination of the country’s overall epidemiology and the epidemiological parameters of antibiotic-resistant bacteria play a crucial role in setting effective prevention and control measures. Hence, the aim of the current meta-analysis is to pool the data from relevant published studies to determine the overall MRSA prevalence in Saudi Arabia.

2. MATERIALS AND METHODS

2.3. Data Extraction

Data from eligible studies were extracted by one reviewer and cross-checked by the second reviewer using data extraction table, disagreements were resolved by discussion and consensus. The extracted data included PubMed identifier number, the name of first author, year of publication, study design, the population studied, type of settings (community or hospital), age, province or city, the total number of subjects, number of MRSA, 95%CI (confidence interval).

3. RESULTS

The present meta-analysis included seven studies according to the selection criteria with a sample size of 8433, one reported data from community settings, five from hospital settings, and one from mixed settings. While according to the region, three studies were from the central region, four from the western region.

The characteristics of the eligible studies including first author, year of publication, sample size, study settings, region, prevalence, 95% CI, and the quality score of the studies (Table 1).

The pooled MRSA prevalence and corresponding 95%CI were also assessed for different subgroups according to the region, where the prevalence of MRSA in the central region including 3 studies, was 32% (95%CI: 21-46) and the western region including 4 studies, was 42% (95%CI: 33-52) (Fig. 3). Studies among these regional subgroups also showed a significant heterogeneity, the western subgroup (Q = 22.31; P˂0.001; I² = 86.55), while the central subgroup (Q = 20.90; P ˂ 0.001; 90.43).

3.1. Publication Bias

The publication bias was assessed using funnel plot, Begg’s and Mazumdar’s rank correlation test, and Egger’s test. The funnel plot did not show any evidence of publication bias, (Fig. 4). The results of Begg’s test (Z = 0.45, P = 0.652) and Egger’s test (t = 3.29, P = 0.22) indicating absence of publication bias.

4. DISCUSSION

The selective pressure for mutated and possibly antibiotic-resistant bacteria which is created by the use, overuse, and misuse of antibiotics for treating both human and animal infections has proven to be worrisome both medically and economically on the global level [29]. The nosocomial and community-associated MRSA strains have emerged as a serious threat, as they acquire genes that make them resistant to nearly all beta-lactam antibiotics, and are becoming increasingly resistant to non-beta-lactam antibiotics [9]. In the Arabian Peninsula as general and Saudi Arabia in particular, MRSA is emerging as a serious health issue, with a number of studies reporting prevalence rates ranging between 8-49% [30-35]. The results of meta-analysis reveal that the prevalence rate of MRSA in Saudi Arabia is 38% which falls well within that range, and indicate a significant increase from the previously reported 29.9% [14]. This relatively large prevalence can be attributed to the fact that Saudi Arabia is a destination for a large number of immigrants and pilgrims including potential carriers of the drug-resistant bacteria. Although it is normal for a bacterial strain to undergo mutations and genetic transformations leading to the development of drug resistance, but the problem is aggravated by a number of contributing factors, such as antibiotics misuse, and the prescription of the drug based on clinical judgment only with no or seldom use of antibiotic sensitivity tests or other appropriate diagnostic procedures. It worth noting that the significant heterogeneity observed in the present meta-analysis can be explained by the differences in the population of the included studies. In an attempt to resolve the heterogeneity issue, we calculated the pooled prevalence based on the region. The included studies focused on two main regions in Saudi Arabia, namely, central and western region. A prevalence rate of 42% was noted in the western region and 32% in the central region. The high prevalence rate in the western region can be explained by the fact that this region is over-populated by immigrants from a number of Asian and African countries. The region also witnesses a large influx of pilgrims during the time of the Islamic pilgrimage, among whom a significant number might be infected or carriers of MRSA. Thus, it is evident that MRSA constitutes a major public health concern in Saudi Arabia, which necessitate the application of strict infection control guidelines, and community-oriented policies and campaigns to increase the public awareness of the risks of the uncontrolled use of antibiotics.

CONCLUSION

In this study, the MRSA prevalence rate in Saudi Arabia is considerably high, with a significant proportion of the cases detected in the western region of the country, given the multi-national nature of the population in that region and the fact that this region represents a very busy commercial and religious hub for people from all over the world. The findings of this study emphasize the urgent need for comprehensive screening, preventive, and educative strategies to control the increasing MRSA prevalence rate. Since this current study included studies that covered the central and western region of the country, future studies that cover the entire country are recommended to show the comprehensive picture of MRSA prevalence in Saudi Arabia.

REFERENCES