Prevalence, trend and antimicrobial susceptibility of Methicillin ...

G Model JIPH-901; No. of Pages 8

ARTICLE IN PRESS Journal of Infection and Public Health xxx (2018) xxx–xxx

Contents lists available at ScienceDirect

Journal of Infection and Public Health journal homepage: http://www.elsevier.com/locate/jiph

Prevalence, trend and antimicrobial susceptibility of Methicillin Resistant Staphylococcus aureus in Nigeria: a systematic review Usman Abubakar a,b,∗ , Syed Azhar Syed Sulaiman a a b

Department of Clinical Pharmacy, School of Pharmaceutical Sciences, Universiti Sains Malaysia, Malaysia Ibrahim Badamasi Babangida Specialist Hospital, Minna, Nigeria

a r t i c l e

i n f o

Article history: Received 2 November 2017 Received in revised form 28 May 2018 Accepted 29 May 2018 Keywords: Methicillin Resistant Staphylococcus aureus Prevalence Antimicrobial susceptibility Nigeria Systematic review

a b s t r a c t Background: Evidence to demonstrate the prevalence and trend of Methicillin Resistant Staphylococcus aureus (MRSA) infection in Nigeria is scarce. This review evaluates the prevalence, trend and antimicrobial susceptibility of clinical MRSA isolates reported in published studies. Method: Electronic search (PubMed, Scopus and Google scholar) was conducted using the following search terms: “MRSA OR Methicillin Resistant Staphylococcus aureus AND Nigeria.” Reference list of selected studies was scanned to identify more studies. Studies published between 2007 and 2017 that tested at least 30 non-duplicate S. aureus isolates were selected. An independent reviewer extracted data from the studies using a standardized form. Results: Twelve studies were included in this review. Overall, prevalence of MRSA infection increased from 18.3% (2009) to 42.3% (2013). The prevalence of MRSA infection was less than 50% in all the regions during the period under review. There was a decline in the prevalence of MRSA infection in the NorthEast (from 12.5% to 8.0%) between 2007 and 2012, and an increase in the South-West (from 20.2% to 47.4%) between 2006 and 2010. Wound, blood and urine specimens had the highest proportion of MRSA isolates. Non-susceptibility of MRSA strains to cotrimoxazole and tetracycline was greater than 85%. Conclusion: Prevalence of MRSA infection in Nigeria is rising, albeit regional variations. Non-susceptibility to commonly prescribed, orally available and inexpensive antibiotics was high. Antimicrobial resistance surveillance system, infection control, and antimicrobial stewardship interventions are recommended. © 2018 The Authors. Published by Elsevier Limited on behalf of King Saud Bin Abdulaziz University for Health Sciences. This is an open access article under the CC BY-NC-ND license (http:// creativecommons.org/licenses/by-nc-nd/4.0/).

Contents Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00 Method . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00 Eligibility criteria . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00 Information sources and search strategies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00 Study selection . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00 Data extraction process . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00 Scope of the study . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00 Results . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00 Studies that combined specimens collected from northern and southern Nigeria . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00 Studies that included S. aureus isolates collected in northern Nigeria . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00 Studies that included S. aureus isolates collected in southern Nigeria . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00 Trend of MRSA infection in Nigeria . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00 Trend of MRSA infection in Northern Nigeria . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00 Trend of MRSA infection in Southern Nigeria . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00

∗ Corresponding author at: Department of Clinical Pharmacy, School of Pharmaceutical Sciences, Universiti Sains Malaysia, 11800 Minden, Penang, Malaysia. E-mail address: [email protected] (U. Abubakar). https://doi.org/10.1016/j.jiph.2018.05.013 1876-0341/© 2018 The Authors. Published by Elsevier Limited on behalf of King Saud Bin Abdulaziz University for Health Sciences. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Please cite this article in press as: Abubakar U, Sulaiman SAS. Prevalence, trend and antimicrobial susceptibility of Methicillin Resistant Staphylococcus aureus in Nigeria: a systematic review. J Infect Public Health (2018), https://doi.org/10.1016/j.jiph.2018.05.013


ARTICLE IN PRESS U. Abubakar, S.A.S. Sulaiman / Journal of Infection and Public Health xxx (2018) xxx–xxx

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Distribution of MRSA infection based on anatomical sites . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00 Antimicrobial susceptibility of clinical MRSA isolates . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00 Discussion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00 Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00 Funding . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00 Competing interests . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00 Ethical approval . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00

Introduction

Method

Methicillin Resistant Staphylococcus aureus (MRSA) infection is a major public health problem in many countries around the world. MRSA is a major cause of healthcare and community acquired infections [1–4]. It causes a wide range of infections including: bacteremia, pneumonia, meningitis, endocarditis, skin and soft tissue, surgical site, urinary tract, bone and joint infections, and toxic shock syndrome [2–6]. Infections caused by MRSA are associated with significant morbidity, mortality and costs [3,7–10]. In Europe, bloodstream MRSA infection occurred in more than 170,000 patients in 2007 with 5,400 deaths reported. The economic burden associated with this infection was estimated as D 380 million [10]. The Centre for Disease Control and Prevention reported that more than 80,000 bloodstream MRSA infections with 11,285 deaths were reported in the United States in 2011 [9]. In Hong Kong, 32.3% of patients diagnosed with MRSA bacteremia die and the direct cost of treatment was $10,565 per patient [3]. The clinical and economic burden of MRSA infection in developing countries is unknown. However, it is thought to be similar or higher than developed countries. The prevalence of MRSA infection in developed and developing countries varies. A recent study highlighted that the prevalence of non-invasive MRSA infection in Germany has declined [4]. Evidence showed that the prevalence of MRSA bloodstream infection in the United States and Europe has declined in recent years [11]. Similarly, MRSA infection rate in Asia is also trimming down [12]. In contrast, the prevalence of MRSA in most African countries is rising, although rate is still below 50% [13]. Changing trajectory of MRSA infection in developed countries is attributed to implementation of control interventions [12,14]. Surveillance of antibiotic resistance is a prerequisite to design and implement effective interventions. Knowledge of the incidence/prevalence and trend of MRSA infection can be used to guide choice of empirical antibiotic therapy, identify priority areas for intervention and serve as a baseline for measuring the impact of interventions [15]. The emergence and spread of MRSA strains with reduced susceptibility to non beta-lactam (glycopeptides and new therapies) has escalated the problem by shrinking treatment options [1,12,14]. Although, MRSA infection is a global problem, there is greater concern in low-income countries where the burden of infectious diseases is high, and effective antibiotics (vancomycin, linezolid, daptomycin, tigecycline) are not readily available. When these antibiotics are available and accessible, they are usually expensive and unaffordable [16]. In addition, some of these antibiotics are associated with toxicity that requires monitoring further making management of MRSA infection difficult. In Nigeria, surveillance data that describes the trend of MRSA in clinical isolates over a period of time is scare. Such data is needed to guide public health policy for the containment of antimicrobial resistance. Therefore, the purpose of this review was to examine the prevalence, trend and antimicrobial susceptibility of MRSA isolates in Nigeria.

This systematic review was conducted and reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Statements [17]. Eligibility criteria Nigerian studies that reported the prevalence and/or antimicrobial susceptibility of Methicillin Resistant S. aureus (MRSA) among clinical isolates of S. aureus were considered for inclusion. Only studies published from January 2007 onward which included nonduplicate isolates were selected. Studies that tested less than 30 S. aureus isolates were excluded. This arbitrary cut-off was consistent with World Health Organization surveillance report regarding antimicrobial resistance. Studies that tested less than 30 bacteria isolates do not adequately represent the proportion of resistant pathogens [18]. Studies that reported the prevalence of MRSA in non-human isolates were also excluded. Information sources and search strategies PubMed and Scopus databases were searched in July 2017 to identify eligible studies. The following search terms were used “MRSA OR Methicillin Resistant Staphylococcus aureus AND Nigeria.” Last search date was 03/08/2017. In addition, the following search words were applied in Google scholar; “MRSA Nigeria”, “Methicillin Resistant Staphylococcus aureus Nigeria,” to identify more studies for inclusion. Furthermore, the reference lists of the identified studies were checked for additional studies. Study selection An independent reviewer screened the title and abstract of identified studies for eligibility. The full texts of the shortlisted studies were assessed using the inclusion criteria described above. Data extraction process A data extraction form was designed and piloted on 5 randomly selected studies. The data collection sheet was refined accordingly. An independent reviewer extracted the following information from the selected studies; first author’s name, year of publication, study design, study setting, study participants, study period, number of S. aureus isolates with the number and proportion of MRSA isolates, type of specimen or focal infection, method employed for the detection of MRSA, and antimicrobial susceptibility of MRSA isolates. The second reviewer checked the extracted data in an effort to minimize errors and bias. Disagreements between the two reviewers were resolved by dialogue. Scope of the study The scope of this review was limited to prevalence, trend, and antimicrobial susceptibility of MRSA infections in Nigeria.




Databases searched: PubMed and Scopus

Search result (n = 114)

Articles included (n = 7) Additional articles identified from Google scholar (n = 4) Additional articles identified through hand search of reference lists (n = 1)

Total articles selected (n =

3

from wound, blood and urine specimens and the overall prevalence of MRSA was 42.3% with higher rate in urine, blood and wound isolates [30]. Table 1 summarizes the characteristics and results of the studies.

Studies that included S. aureus isolates collected in northern Nigeria Northern Nigeria comprises of 3 zones; North-West, NorthCentral and North-East. Three studies reported prevalence of MRSA infection in the Northern region. The first study included 96 S. aureus isolates collected from 6 tertiary hospitals in North-Eastern Nigeria. The prevalence of MRSA was 12.5%. This prospective (January–December 2007) study included S. aureus collected mostly from wound and urogenital specimens. MRSA strains were isolated from wound (9), genital swab (2) and eye (1) specimens [24]. The second study was conducted in the same region (NorthEast) and involved 75 S. aureus isolates mostly from wound and urine specimens. The prevalence of MRSA infection was 8% [25]. The third study screened 214 S. aureus isolates collected between April 2010 and June 2011; the rate of MRSA infection was 13.1%. Most of the MRSA isolates were from blood, wound and urine specimens. More than 70% of MRSA strains were isolated from inpatient specimens [27]. Table 1 describes the characteristics and results of the studies.

12)

Fig. 1. Flow diagram of the study selection process for inclusion in the review.

Results PubMed and Scopus databases search identified 114 articles. Out of those, 7 articles were selected. Four additional articles were identified and selected through Google scholar search. Furthermore, one article was identified through hand search of reference lists. In the end, 12 articles were included in this review. Details of the screening process for identification and inclusion of studies are provided in Fig. 1. The selected studies were all prospective in nature. Five of the studies were conducted in South-West [19–23]; 2 in NorthEast [24,25]; and 1 each in South-South [26] and North-Central [27]. There was no article from the North-West and South-East region that satisfied the eligibility criteria. Three of the studies combined S. aureus isolates collected from Northern and Southern parts of Nigeria [28–30]. Antimicrobial susceptibility of MRSA isolate was reported in 8 studies [19,21,23,24,26–29]. This review included a total of 2203 S. aureus isolates and 582 were MRSA strains. Studies that combined specimens collected from northern and southern Nigeria There were three (3) studies that combined S. aureus isolates collected from northern and southern Nigeria. The first was a prospective study conducted in 4 tertiary hospitals (3 in SouthWest and 1 in North-East) between January and April 2009. This study included 60 clinical S. aureus isolates, and the prevalence of MRSA was 18.3% as determined using oxacillin and confirmed with detection of mecA gene through polymerase chain reaction (PCR) [29]. The second study found that 15 (16.5%) out of the 91 clinical isolates possesed mec A gene. This study was conducted between January and April 2010 [28]. The third study reported the prevalence of MRSA in 4 tertiary hospitals (3 in the South-West and 1 in North-Central). The study included 156 clinical S. aureus isolates collected between March and June 2013. Most of the isolates were

Studies that included S. aureus isolates collected in southern Nigeria Southern Nigeria also encompasses 3 geographic zones; SouthWest, South-South and South-East. In the South-South, a single centre study revealed that the prevalence of MRSA infection was 42.7%. This study included 522 S. aureus isolates, and most of the isolates (>90%) were cultured from wound swabs and pus specimens [26]. Five studies described the prevalence of MRSA infection in South-West Nigeria. A multicenter study conducted across 2 states reported an MRSA rate of 22.1%. There were 194 S. aureus isolates mostly from wound, urine and eye specimens [19]. Another prospective bicentric study found that 41.4% of 116 S. aureus isolates possessed the Mec A gene which codes for resistant in MRSA. Prevalence of MRSA was higher among female patients [23]. The third study involved 217 clinical S. aureus isolates and found that 2.3% were resistant to oxacillin and possesed the mec A gene. Most of the S. aureus isolates were collected from skin and soft tissue, wounds, otitis media and urinary tract infections [20]. The fourth study demonstrated that 47.4% of S. aureus isolates were positive for mecA gene [22]. The 5th study involved two hospitals in one state and revealed that 20.3% of the 346 S. aureus isolates were resistant to methicillin. Majority of the MRSA strains were isolated from surgical and paediatric units. Higher proportion of MRSA was detected in surgical wound infection, followed by ear and eye swabs and skin and soft tissue infections [21]. Table 1 illustrates the characteristics of the included studies.

Trend of MRSA infection in Nigeria Available evidence demonstrated that the prevalence of MRSA infection in Nigeria has increased. The rate was reported as 18.3% in 2009, 16.5% in 2010 and 42.3% in 2013 [28–30]. It could be inferred based on these surveillance data that rate of MRSA infection has increased from 18.3% in 2009 to 42.3% by 2013 (representing a 2.3 fold increase). All the studies utilized Polymerase Chain Reaction (PCR); the gold standard method, for detection of MRSA isolates.


Type of specimen/infection

Percentage of MRSA among S aureus isolates n/N (%)

Distribution and proportion (%) of MRSA based on specimen type

Method used for detection of MRSA

Ghebremedhin, 2009 [21]

Prospective, MC, 2006–2007

South-West, inpatients and outpatients

Wound, ear/eye swab, genital swab, nasal swab

70/346 (20.2%)

Wound 37 (52.8) Ear/eye swab 19 (27.1) SSTI 14 (20.0)

Okon, 2011 [24]

Prospective, MC, January–December 2007

North-East, inpatients and outpatients

12/96 (12.5)

wound 9 (75) HVS/ECS 2 (16.7) Eye 1 (8.3)

Shittu, 2011 [29]

Prospective, MC, January–April 2009

North and South, inpatients, outpatients

Wound, HVS/ECS, Urine, ear swab, Pus, urethra, eye, semen, sputum, blood wound, nasal, sputum, ear, eye, semen, urine, blood

Methicillin disc and PCR Cefoxitin disc and PCR

11/60 (18.3)

Wound 5 (45.4) Semen 2 (18.2) Throat, eye, urine and ulcer wound 1 (9.1) each

PCR

Alli, 2011 [19]

Prospective, MC, NR

South-West, inpatients, and outpatients

Urine, blood, ear wound, eye, catheter tip, nasal, ECS, HVS

43/194 (22.1)

Wound 8 (18.6) Urine 6 (13.9) Ear swab 6 (13.9) HVS 6 (13.9) Eye swab 6 (13.9) Nasal 5 (11.6) Catheter tip 4 (9.3) ECS 2 (4.6)

PCR

Shittu, 2012 [28]

Prospective, MC, January–April 2010

North and South, inpatients and outpatients

blood, wound, nasal, ear, eye, SSI, GTI, UTI, osteomyelitis, bronchitis, burns, leg ulcer, prostatis, SLE

15/91 (16.5)

Blood 3 (20.0) Wound 3 (20.0) Bronchitis 2 (13.3) GTI 2 (13.3) Osteomyelitis 2 (13.3) Burns 1 (6.7) Ear 1 (6.7) Nasal 1 (6.7)

Oxacillin disc and PCR

Terry Alli, 2012 [23]

Prospective, bicentric, NR


Wound, urine, aspirate, ear, eye ECS, urethral swabs

48/116 (41.3)

Wound 12 (25.0) Urine 12 (25.0) Ear and eye 8 (16.7) Blood and aspirate 7 (14.6) ECS 4 (8.3) Urethral swab 4 (8.3)

PCR

Akanbi, 2012 [27]

Prospective, MC, April 2010–June 2011

North-Central, inpatients and outpatients

Wound, Urine, blood, vagina, hair scalp, skin, ear, CSF

28/214 (13.1)

Blood 11 (39.3) Wound 7 (25.0) Urine 4 (14.3) Skin 4 (14.3) CSF 2 (7.1)

Oxacillin disc

Okon, 2014 [25]

Prospective, MC, 2012

North-East, inpatients and outpatients

Wound, urine, ear and blood

6/75 (8)

NR

PCR

Alli, 2015 [30]

Prospective, MC, March–June 2013

North and South, inpatients and outpatients

wound, blood, ear and eye, urine, others (catheter tip, aspirate, HVS)

66/156 (42.3)

Blood 20 (30.3) Wound 14 (21.2) Urine 14 (21.2) Ear & eye 8 (12.1) Others 10/24 (41.6)

Cefoxitin disc and PCR

ARTICLE IN PRESS

Location and type of participants

G Model

Study design, setting, period

U. Abubakar, S.A.S. Sulaiman / Journal of Infection and Public Health xxx (2018) xxx–xxx

First author, year

JIPH-901; No. of Pages 8

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Table 1 Characteristics and the prevalence of MRSA reported in individual studies.

Location and type of participants

Type of specimen/infection

Percentage of MRSA among S aureus isolates n/N (%)

Distribution and proportion (%) of MRSA based on specimen type

Method used for detection of MRSA

Ayepola, 2015 [20]

Prospective, MC, 2010–2011

South-West, inpatients

SSI, RTI, wound, otitis media, UTI, conjunctivitis, septicaemia, vaginitis, nasal swab

5/217 (2.3)

NR

PCR

Yusuf, 2015 [26]

Prospective, SC, September 2013–November 2014

South-South, inpatients and outpatients

Wound, pus, blood, sputum, urine and body fluid

223/522 (42.7)

NR

Rapid latex agglutination test

Ogbolu, 2015 [22]

Prospective, MC, January–December 2010


Wound, urine, blood, ECS, eye, catheter tip, aspirate, nasal, urethral swab, semen

55/116 (47.4)

Urine 16 (29.0) Wound 14 (25.4) Blood 6 (11.0) ECS 6 (11.0) Eye 5 (9.1) Aspirate 5 (9.1) Urethral 2 (3.6) Catheter 1 (1.8)

PCR

MC: multicentre, SC: single centre, SSTI: skin and soft tissue infection, PCR: polymerase chain reaction, HVS: high vaginal swab, ECS: endocervical swab, SSI: surgical site infection, GTI: genital tract infection, SLE: systemic lupus erythematosus, CSF: cerebrospinal fluid, RTI: respiratory tract infection, NR: not reported.

ARTICLE IN PRESS

Study design, setting, period

G Model


First author, year



Table 1 (Continued)

5

G Model

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6

Trend of MRSA infection in Northern Nigeria Surveillance data illustrated that the prevalence of MRSA infection in North-East Nigeria has declined from 12.5% in 2007 to 8% in 2012 [24,25]. Only one study reported incidence of MRSA infections in North-Central Nigeria and the rate was 13.1%. There was no surveillance data from North-West Nigeria that was included in this review. Therefore, there are no data to demonstrate the trend of MRSA infections in this region.

This finding was not in consonant with trend reported in South Africa where evidence showed a 12% reduction in the prevalence of MRSA infection (from 36% in 2006 to 24% during 2007–2011). The result of the current review was in agreement with the trend reported in some African countries including; Tunisia (16%–41% between 2002 and 2007), and Algeria (35%–75% during the periods 2003 and 2009) [13]. The decrease in MRSA rate experienced in 2009 could be attributed to natural tendencies or variations in the study settings and specimens. Decelerating trend of MRSA infection in South Africa could be attributed to the establishment of Antimicrobial Resistance Surveillance Network. A functional surveillance system tracks antimicrobial resistance, and identify areas where interventions are needed. Evidence indicated that the implementation of antimicrobial resistance control interventions including: developing national antimicrobial resistance control strategy, establishing antimicrobial resistance surveillance system, developing antimicrobial stewardship programmes, promoting adherence to clinical practice guidelines, and infection control interventions has reduced the trend of MRSA infection in some countries [4,12,31]. Nigeria has no national antimicrobial resistance containment strategy at the moment. There is also no established antimicrobial resistance surveillance system. However, efforts are made to develop and implement such interventions. Lack of these interventions coupled with poor infection control, and inappropriate use of antibiotics could explain the rising trend of MRSA infection in Nigeria. Caution should be applied when comparing our result with other reports because of inter-study variations including; types of isolates, practice settings, periods of study, methods and breakpoint employed for detection of MRSA isolate. These differences could affect the prevalence of MRSA infection reported in different parts of the world. There were regional variations in the trend of MRSA infection in Nigeria; prevalence in the North-Eastern part has reduced whereas the rate in the South-Western part has increased. This contrasting trend may be due to naturally occurring fluctuations. In addition, the variance could be explained by difference in the hospital characteristics (infection control, and antibiotic utilization); number, and source of S. aureus isolates; and method used for detection of MRSA. This review observed that MRSA was implicated in a wide range of infections including: osteomyelitis; bloodstream; skin, and soft tissue; surgical site/wound; respiratory tract; and urinary tract infections. This denotes that MRSA infection could be either Hospital-associated (HA) or Community-associated (CA). CA-MRSA is commonly associated with skin and soft tissue infections while HA-MRSA is implicated in bloodstream; surgical site; respiratory tract; and urinary tract infections [32]. Our review found that wound (18.6%–75%), blood (11%–39.28%) and urine (9.1%–29%) specimens represented the major sources of MRSA isolates in Nigeria. This observation indicates that most MRSA strains

Trend of MRSA infection in Southern Nigeria There was only one study that reported incidence of MRSA infection in South-South Nigeria. The prevalence of MRSA in that zone was 42.7%. No study from the South-East was included in this review. The prevalence of MRSA infection in the South-West increased from 20.2% during 2006–2007 to 47.4% by the year 2010 [21,22]. Distribution of MRSA infection based on anatomical sites Nine studies reported the distribution of MRSA infection based on specimen type or anatomical site. MRSA isolate was detected in wound, cerebrospinal fluid, eye/ear, burn, high vaginal/endocervical, semen, urine, catheter tip, blood and nasal specimens. The distribution varied and wound specimen had the highest proportion; representing 18.6%–75% of all MRSA isolates. This was followed by blood (11%–39.28%) and urine (9.1%–29%) specimens. Table 1 shows the distribution of MRSA isolates based on anatomical site. Antimicrobial susceptibility of clinical MRSA isolates Antimicrobial susceptibility test showed that MRSA isolates were sensitive to mupirocin, daptomycin, linezolid, teicoplanin, tigecycline and fosfomycin. Vancomycin, rifampicin and fusidic acid had excellent susceptibility against MRSA (85%–100%). Susceptibility of MRSA isolates to other antibiotics including; gentamicin (0%–60%), erythromycin (0%–66.7%), cotrimoxazole (0%–13.3%) and tetracycline (0%–13.3%) was relatively low. Sensitivity to fluoroquinolones varied and moxifloxacin (36.4%–93.3%) had higher sensitivity than ciprofloxacin (0%–53.3%) and ofloxacin (0%–25%). Table 2 summarizes the susceptibility of MRSA isolates to antibiotics. Discussion Overall, the prevalence of MRSA infection in Nigeria was less than 50%. This was consistent with the rate reported in most African countries [13]. Available evidence suggested that the prevalence of MRSA infection in Nigeria has increased by 2.3 folds; from 18.3% in 2009 to 42.3% in 2013. However, the increase was not consistent as the prevalence dropped to 16.5% in 2010 and rose to 42.3% by 2013. Table 2 Antimicrobial susceptibility (%) of MRSA isolated from clinical specimen. Author

No. of isolate

Ghebremedhin et al. [21] Shittu et al. [29] Okon et al. [24] Shittu et al. [28] Terry Alli et al. [23] Akanbi and Mbe [27] Yusuf and Airauhi [26] Alli et al. [30]

70 11 12 15 48 28 223 66

GEN

ERY

CIP

18.2 0 60

45.5 0 66.7

27.3 0 53.3

0 0 30

10.7 0

0

OFL

MOX

COT

CLIN

36.4

9.1 0 13.3

45.5 25 66.7

93.3 25 0

VAN 100 100 100 100 100 85.7 100 100

RIF

MUP

FSA

100 100 86.7

100 100 100

100 100 100 93.3

DAP

LIN

TEI

TIG

FOS

100

100

100 100

100

100

100

100

100 100

TET

13.3

0

GEN: gentamicin, ERY: erythromycin, CIP: ciprofloxacin, LEV: levofloxacin, OFL: ofloxacin, MOX: moxifloxacin, COT: cotrimoxazole, CLIN: clindamycin, VAN: vancomycin, RIF: rifampicin, MUP: mupirocin, FSA: fusidic acid, DAP: daptomycin, LIN: linezolid, TEI: teicoplanin, TIG: tigecycline, FOS: Fosfomycin, CCHL: chloramphenicol, NIT: nitrofuratoin, TET: tetracycline.




in Nigeria were HA-MRSA and underlines the importance of antibiotic stewardship, and infection control interventions. Evidence signifies that implementation of hand hygiene and antimicrobial stewardship interventions effectively reduce MRSA infection rate [33]. This review also found that non-susceptibility of MRSA isolates to tetracycline and cotrimoxazole, two of the most commonly used oral antibiotics, was greater than 85%. In contrast, a study conducted in Germany showed that the sensitivity of MRSA isolates to tetracycline and cotrimoxazole was more than 85% [4]. A previous study posited that non-susceptibility of MRSA isolates to tetracycline and cotrimoxazole in Nigeria was due to excessive and inappropriate use of these antibiotics [34]. These antibiotics are purchased by patients without prescription from the pharmacy. Studies included in this review revealed that nonsusceptibility to fluoroquinolones ranged between 6.7%–100%. The European Antimicrobial Resistance Surveillance Network (EARSNet) reported that 85.2% of MRSA isolates were resistant to fluoroquinolones [35]. Another study found that 84%–95% of MRSA isolates were non-susceptibility to fluoroquinolone [4]. Resistance of MRSA to non beta-lactam antibiotics is a cause for concern because it narrows the therapeutic choices. This review observed that all MRSA isolates were susceptible to teicoplanin, linezolid, tigecycline and mupirocin while non-susceptibility to vancomycin ranged between 0%–14.3%. In Germany, MRSA isolates collected between 2010 and 2015 were susceptible to vancomycin, teicoplanin, linezolid, and tigecycline [4]. Our results should be interpreted with caution because studies included in this review may not be representative of the Nigerian population. No study from South-Eastern and North-Western Nigeria was eligible for inclusion. In addition, most of the studies were conducted in tertiary healthcare facilities and may not reflect the prevalence and trend in secondary and primary healthcare centres. The rate of MRSA infection in Nigeria may be over-estimated because microbiological culture and susceptibility test was often requested if empirical antibiotic therapy fails. Therefore, many susceptible S. aureus isolates were not captured. There are interstudy variations in terms of specimen types and method employed for detection of MRSA. Prospective or point-prevalence studies involving multiple centres spread across the 6 geopolitical zones in Nigeria are needed to estimate the current state of MRSA infection in Nigeria. Future multicentre studies should focus on similar infection sites (specimen) and employ standardized methods for isolation and confirmation of MRSA strains. Despite these limitations, this study provides an insight on the prevalence, trend and antimicrobial susceptibility pattern of MRSA infections in Nigeria. A major strength of this review is that 11 out of the 12 studies used molecular methods (ten employed polymerase chain reaction, and one used Rapid latex agglutination test) to confirm MRSA strains. Polymerase chain reaction is a gold standard for confirmation of MRSA isolates [36].

Conclusion The prevalence of MRSA infection in Nigeria has increased from 18.3% to 42.3% between 2009 and 2013 and substantial proportion was isolated from surgical wound specimen. There were regional variations in the trend of MRSA infection; decreasing trend in the North-East, and increasing trend in the South-West. Nonsusceptibility to non-beta lactam antibiotics, particular tetracycline and cotrimoxazole was high. Continuous surveillance of antibiotic resistance, implementation of antibiotic stewardship, and infection control interventions are recommended.

7

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