Acinetobacter infections prevalence and frequency of the antibiotics resistance: comparative study of intensive care units versus other hospital units

Introduction This study aims to determine the Acinetobacter sp clinical isolates frequency and its antibiotic susceptibility pattern by comparing results obtained from the Intensive Care Units (ICUs) to that of other units at the Mohammed V Military Teaching Hospital in Rabat. Methods This is a retrospective study over a 2-years period where we collected all clinical isolates of Acinetobacter sp obtained from samples for infection diagnosis performed on hospitalized patients between 2012 to 2014. Results During the study period, 441 clinical and non-repetitive isolates of Acinetobacter sp were collected representing 6.94% of all bacterial clinical isolates (n = 6352) and 9.6% of Gram negative rods (n = 4569). More than a half of the isolates were from the ICUs and were obtained from 293 infected patients of which 65, 2% (191 cases) were males (sex ratio = 1.9) and the median age was 56 years (interquartile range: 42-68 years). Acinetobacter clinical isolates were obtained from respiratory samples (44.67%) followed by blood cultures (14.51%). The resistance to ciprofloxacin, ceftazidime, piperacillin / tazobactam, imipenem, amikacin, tobramycin, netilmicin, rifampicin and colistin was respectively 87%, 86%, 79%, 76%; 52%, 43%, 33% 32% and 1.7%. The difference in resistance between the ICUs and the other units was statistically significant (p <0.05) except for colistin, tetracycline and rifampicin. Conclusion This paper shows that solving the problem of prevalence and high rate of multidrug resistant Acinetobacter infection which represents a therapeutic impasse, requires the control of the hospital environment and optimizing hands hygiene and antibiotics use in the hospital.


Introduction
Acinetobacter is a non-fermenting Gram negative coccobacillus with a high capacity to colonize the human body and the environmental reservoirs [1]. It has become over the past three decades a major associated care infections agent with a high morbidity and a high mortality rate especially in immunocompromised patients ranging from 26.5 to 91% [2][3][4][5]. In Morocco, a retrospective study [6] from 2002 to 2005 showed that this bacterium represented 13.63% of clinical isolates from blood cultures in the intensive care units (ICUs) [6] and in another Moroccan study [7], it represented 6.74% of all Gram-negative bacilli. The Acinetobacter infection prevalence is variable depending on the geographical localization and the patient's socio-economic status [8][9][10]. In an international study in ICUs, the Acinetobacter infections rate was 19.2% in Asia; 17.1% in Eastern Europe; 14.8% in Africa; 13.8% in Central and South America; 5.6% in Western Europe; 4.4% in Oceania and 3.7% in North America [10]. It is 15% in South African HIV-positive patients [8] and 13% in Canadian burn care units [9]. In our region, no studies on Acinetobacter prevalence have been performed. Acinetobacter is an opportunistic pathogen known for its intrinsic resistance to antibiotics and greater ability to rapidly acquire resistance genes as mobile genetic elements (plasmids, transposons, integrons cassettes and insertion sequences) [11][12][13].
Multidrug resistant (MDR) Acinetobacter baumannii is becoming a global threat with a therapeutic impasse increasingly described in literature [14][15][16]. Indeed this organism generally has resistance to several antibiotics. According to the literature data, the resistance rate varies from 31

Characteristics of Acinetobacter´s clinical isolates
During the study period, 441clinical isolates of Acinetobacter were collected, representing 6.94% of all bacterial isolates (n=6352) and 9.6% of all Gram-negative bacilli (n=4569) throughout the hospital.

Discussion
The present study shows that the infection Acinetobacter 's prevalence in HMIMV is high with higher rates in ICUs compared to other units (p <0.001). The isolation rate of Acinetobacter in the various samples was 6.94%.These results are higher compared to those from the study conducted by Mushtaq and al. (2013) [14] in Pakistan where the isolation rate of Acinetobacter species was 4.2% [11]. In an international study on the prevalence of infections in ICUs in 75 countries [10], the isolation rate of Acinetobacter ( study is probably related to non-compliance with the recommendations for mastery the hospital environment [24], lack in hands hygiene and misuse of antibiotics [25]. Some studies have reported that this microorganism which has emerged worldwide as a pathogen causing serious infections in hospitalized patients has the ability to persist in the environment for a long period of time, colonize patients or healthy subjects and can develop into a true infection at any time [26]. Since hand transmission is a major factor in the spread of this pathogen [24], hand hygiene and disinfection of equipment/environment are the two most important factors to control and prevent the outbreak of an epidemic Acinetobacter [24].  [18,21]. Carbapenem resistance in A. baumannii is often due to the expression of OXA carbapenemase types, Metallo-beta-lactamases (MBL) carbapenemase and the impermeability associated with mutations altering the expression of porins and efflux pumps [3,30]. In this study, most of the Acinetobacter strains showed the phenotype having resistance to beta-lactam antibiotics associated with the expression of carbapenemase or alteration of porins (63, 1%). These results are not in accordance with those found in another study conducted in the same hospital where the penicillinase phenotype and high level Page number not for citation purposes 5 cephalosporinase production were predominant with a rate of 33% [22]. In a Tunisian study, the majority of A. baumannii trains had the penicillinase phenotype in 26.3% of cases [19]. This emphasizes the alarming increase in resistance to imipenem and the expression of carbapenemase often related to the misuse of this antibiotic class in the clinical departments of our hospital. For the aminoglycosides, netilmicin was the most effective with a resistance rate of 33.07% against 43.03% for tobramycin and 52.28% for amikacin. Our data are different and lower than those obtained by Jaggi and al. (2012) in India; where resistance to tobramycin, gentamicin, netilmicin and amikacin were 80.0, 85.8, 90.3 and 90.3% respectively [19]. The aminoglycosides resistance in Acinetobacter spp. involves the production of aminoglycosides modifying enzymes and genes encoding these enzymes can be acquired through plasmids, transposons or integrons [3,20]. The rate of resistance to ciprofloxacin observed in our study (87.7%). This rate is comparable to that reported in the literature which varies from 28.8 to 91.6% [8,[17][18][19][20]. The prescription of this drug in the treatment of Acinetobacter infections is rare because of the high resistance to this antibiotic in our institution. Rifampicin was very effective (but less than colistin) with a resistance rate of 32.11%, but the use of this drug in the treatment of Acinetobacter infections is limited because Morocco is a country of endemic tuberculosis. Colistin was the most active antibiotic against Acinetobacter. In this study, the resistance to colistin was 1.7%.
Some studies have reported that no clinical isolate of Acinetobacter was resistant to colistin [13,22] but the resistance to colistin has been described in India, South Africa and Korea [20,33]. Several authors confirm that colistin remains the only option for empirical treatment of serious Acinetobacter infections in cases where this bacterium is strongly suspected to be resistant to other antibiotics [12,19]. The mechanism of resistance to this antibiotic is rare and may be explained by the loss of lipopolysaccharide and/or deployment of a system of twocomponent regulatory PmrAB [34,35]. Synergy between colistin and rifampicin or anti-Pseudomonas carbapenem is described in some studies [25]. There are no specific recommendations regarding the combination of antibiotics for the treatment of these serious infections due to the lack of prospective comparative clinical trials with a control group [25]. The combination therapy used in

Conclusion
In this study, we showed that, in our hospital, the frequency and rates of MDR Acinetobacter infection are high and could pose a real problem and a management impasse. A strict control of the hospital environment, hand hygiene and optimizing the use of antibiotics is recommended in order to reduce the MDR frequency.
What is known about this topic  Acinetobacter is a non-fermenting Gram negative coccobacillus with a high capacity to colonize the human body and the environmental reservoirs and it is associated with a high morbidity and a high mortality rate especially in immunocompromised patients.
 Acinetobacter is an opportunistic pathogen known for its intrinsic resistance to antibiotics and greater ability to rapidly acquire resistance genes.
 It generally has resistance to several antibiotics and MDR Acinetobacter baumannii is becoming a global threat

Competing interests
The authors declare no competing interests.

Authors' contributions
UJ, EM and IA designed the study, drafted the manuscript, analyzed and interpreted the data. FM, LA, BF, BB and SD performed the laboratory work. AM LB, AB, HC, LL contributed to samples collection. All authors read and approved the final manuscript.