uring the course of management of bacterial infections, bacteria might develop the ability to resist the bactericidal or bacteriostatic effects of one or more antibiotic class (multidrug resistance (MDR)) [1]. This is usually a result of the frequent and widespread use of potent antibiotics, which is the main reason why antimicrobial resistance is more noted in the intensive care units (ICUs) in comparison to the other inpatient departments in hospitals worldwide [2]. According to the national healthcare safety network report in the United States, host risk factors for developing a nosocomial infection are age, comorbid diseases, duration of hospitalization, length of ICU stay, immune status, and disease severity. It was reported that the incidence of ICU nosocomial infections worldwide is between 5%-30% [3]. A study conducted in 8 European countries concluded that overuse was one of the factors associated with increased antibiotic resistance [4].

The patterns of antimicrobial resistance vary between ICUs in different countries due to the various factors leading to such a resistance including different patterns of infections and antibiotic use, the variations in local infection control policies, and the effective usage of the local resistance reports directing the suitable antibiotic therapies in practice, all of which will lead to different resistance patterns, and outcomes on patients and healthcare systems accordingly [5]. Over the past few years, the efficacy of antibiotics against various ICU pathogens has been decreasing, with MDRs on the rise [6]. Globally, Antibiotic resistance is still a continuous issue however due to the differences in international and national data, a local continuous surveillance studies should be conducted to identify the emergence of different bacterial resistance patterns in order to establish local guidelines. This study was done to estimate the prevalence of Gram-positive infections in intensive care units (ICU), and to observe the patterns of resistance against different antibiotics.

A cross-sectional retrospective study was conducted on Gram-positive isolates from the adult ICU of King Abdulaziz Medical City (KAMC) between the period of 2010 and 2014. The ethics committee and institute review board in King Abdullah International Medical Research Centre approved this project.

The annual antibiogram data was used to calculate the percentage of resistance in Gram-positive bacteria with a total of 2155 isolates from blood, urine, sputum and respiratory aspiration. All isolates were analyzed per the guidelines of the Clinical and Laboratory Standards Institute (CLSI).The species level and AST performed using an automated system (The VITEK®2 system, BioMariex, France) to characterize all Gram-positive bacteria. All antimicrobial susceptibility testing was confirmed by manual method. Only one isolate per patient per year was used for analysis. Ampicillin, ceftazidime, ceftriaxone, ciprofloxacin, gentamicin, imipenem, and trimethoprimsulfamethoxazole were tested either by the breakpoint method (with the vitek 2 system) or by the ETEST method using the previously mentioned antibiotics on a Muller Hinton Agar Plate. The proportion of susceptible isolates was calculated as the sum of susceptible organisms (neither intermediately susceptible nor resistant) relative to the total number of organisms tested. Multidrug resistance was defined as resistance to three or more antimicrobials (imipenem, ceftazidime, ciprofloxacin, pipracillin-tazobactam, and/or an aminoglycoside).

The trend in the resistance rate over a 5-year period (between 2010-2014) was analyzed to identify a statistically significant increasing or decreasing trend using chi-square for linear trend analysis and chi-square test was used for testing the association between categorical variables. The percent of change of antibiotic susceptibility was calculated as the difference between the later (e.g. 2014) and earlier (e.g. 2010) susceptibilities percentages divided by the earlier one. P value <.05 was considered as statically significant. All P values were two-tailed. SPSS software package for Windows (version 22.0, IBMCorp, Armonk, NY, USA) was used for all statistical analyses III.

From 2010 to 2014, there were 6611 isolated organisms in total, out of which 2155 (33%) were Grampositive. There were 285 Gram-positive organisms isolated in 2010, 294 in 2011, 334 in 2012, 632 in 2013, and 610 in 2014. Among all isolated Gram-positive organisms, methicillin-susceptible Staphylococcus aureus (MSSA) were the most commonly isolated 849 (39%) followed by Enterococcus 590 (27%), methicillinresistant Staphylococcus aureus (MRSA) 462 (21%), Streptococcus pneumoniae 135 (6%), Coagulase negative Staphylococcus 113 (5%), and Streptococcus viridans 6 (0.27%). All screening samples were not included to avoid false representation of colonization rather than true infection.

Over the study period, MSSA resistance increased to clindamycin until 2013 (5% to 12%, p=0.15), erythromycin (5% to 13%, p=0.001), and trimethoprim/sulfamethoxazole(TMP/SMX) (1% to 4%, p=0.19). There was no resistance to vancomycin, and penicillin throughout the study period (0%), however, from 2010 to 2013, MSSA was 100% resistant to moxifloxacin.

Of 590 Enterococcus isolates, there was an increase in ampicillin (59% to 71%, p=0.003), and in vancomycin resistance (37% to 46%, p=0.170); a decrease in the resistance to ciprofloxacin, and nitrofurantoin (96% to 76% and 66% to 54%), respectively.

MRSA resistance decreased to clindamycin (72% to 52%, p<0.0001), erythromycin (72% to 53%, p<0.0001), and TMP/SMX (60% to 46%, p<0.0001). However, no change was seen in MRSA resistance to cefazolin (1%) from 2012 to 2014, and to vancomycin (0%) throughout the study period.

Streptococcus pneumoniae showed a significant decrease in resistance to cefotaxime (50% to 0%, p=0.003); an increase in resistance to erythromycin (25% to 50%, p=0.428), and to penicillin (0% to 7%). On the other hand, there was no change in the resistance to moxifloxacin, and vancomycin (0%) throughout the study period.

Coagulase negative Staphylococcus showed significant increase in the resistance to cefazolin (54% to 90%, p<0.0001), and erythromycin (65% to 90%, p=0.02). On the other hand, Coagulase negative Staphylococcus resistance to TMP/SMX decreased (62% to 20%, p=0.001) and showed no resistant to vancomycin from 2010 to 2014.

Antimicrobial resistance is a global concern [1]. ICU is a potential source of multidrug resistance due to the widespread use of multiple antibiotics compared to other hospital departments [2]. Methicillin sensitive Staphylococcus aureus was found to be the most commonly isolated organism in the adult ICUs of KAMC (849 isolates). Savas et al. reported that from 597 ICU isolates, 241 were Staphylococci, and MSSA was not the most common isolates 24 (9.96%) [7]. In this study, among 1,424 Staphylococcus isolates, MSSA was the most commonly isolated organism 849 (59.6%). Savas et al evaluated the resistance of MSSA to clindamycin, erythromycin, and TMP/SMX, and it was 25%, 27%, and 21%, respectively [7].Looking at the ranges of MSSA resistance in this study, MSSA resistance increased to clindamycin (5% to 12%), erythromycin (5% to 13%), and TMP/SMX (1% to 4%). In our study, vancomycin, and cefazolin remain the most effective antibiotics against MSSA. Comparison of the overall resistance pattern is illustrated in table-1.

Although MRSA is considered an endemic in many hospitals worldwide, it is still difficult to be eradicated, and remains a major concern in all ICUs [8].MRSA is showing a significant increase in prevalence in many ICUs reaching to 60% of all isolates [9]. In this study, from 2010 to 2014 and among 2155 Grampositive isolates, MRSA were the third most common isolates in KAMC adult ICU 462 (21%).Vancomycin is considered the most important antibiotic used for MRSA till date [10].However, MRSA showed a resistance against vancomycin in other reported studies [10].Fortunately enough, throughout our study period, MRSA showed no resistance to vancomycin in KAMC adult ICUs. Comparison of the overall resistance pattern is illustrated in table-1.

Enterococci are considered one of the most common causes of hospital-acquired infections. In the past 20 years, Enterococci have become increasingly resistant to many antibiotics [9]. Recent studies conducted to assess the incidence of multidrug resistant Gram-positive pathogens showed that Enterococcusfaecalis accounted for 15.7% of all Grampositive isolates. In our study, we found that 27% of all Gram-positive isolates were Enterococcus. Hällgren A et al. Evaluated the resistance of Enterococcusfaecium to ampicillin, vancomycin, and ciprofloxacin and it was 74.3%, 1.4%, and 82.4% respectively [11]. In this study the resistance pattern of Enterococcus to ampicillin, and ciprofloxacin was almost the same as the resistance that was reported by Hällgren A et al., 71% and 76% respectively. However, Enterococcus was highly resistant to vancomycin 46%. V.

Our study revealed that antibiotic resistance among Gram-positive organisms remains a continuous issue in adult ICU, KAMC-Riyadh. Among all isolated Gram-positive organisms, the most commonly isolated were MSSA (39%), Enterococcus (27%), and MRSA (21%). Vancomycin remains the most effective drug against MSSA, MRSA, Streptococcus pneumonia, and Coagulase-negative Staphylococci. The overuse of multiple antibiotics in ICU is considered one of the reasons behind the significant resistance. Therefore, strict adherence to infection prevention guidelines and continuous monitoring to antimicrobial resistance are essential to avoid major outbreak in the future.

Limitation: This study was conducted in a single center in Riyadh (KAMC) and in a limited period of time 2010-2014 which could be considered as a limitation to our findings.In addition, the data was collected from the yearly antibiogram. Therefore, Patients data such as age, sex and antibiotic use were not possible to obtain to study some of the risk factors