Prevalence of extensively drug-resistant gram negative bacilli in surgical intensive care in Egypt

Introduction The prevalence of extensively drug resistant gram negative bacilli (XDR-GNB) is rapidly progressing; however in Egypt data are sparse. We conducted the present study to quantify the incidence, risk factors and outcome of patients harboring XDR-GNB. Methods A one year prospective study was done by collecting all the bacteriological reports for cultures sent from the surgical intensive care unit, Cairo university teaching hospital. XDR-GNB were defined as any gram negative bacilli resistant to three or more classes of antimicrobial agents. Patients with XDR-GNB compared with those sustaining non extensively drug-resistant infection. A multivariate logistic regression model was created to identify independent predictors of multi-resistance. Results During one-year study period, a total of 152 samples (65%) out of 234 gram negative bacilli samples developed extensively drug resistant infection. XDR strains were significantly higher in Acinetobacterspp (86%), followed by Pseudomonas (63%), then Proteus (61%), Klebsiella (52%), and E coli (47%). Fourth generation cephalosporine (Cefipime) had the lowest susceptibility (10%) followed by third generation cephalosporines (11%), Quinolones (31%), Amikacin (42%), Tazobactam (52%), Carbapinems (52%), and colistin (90%). Relaparotomy was the only significant risk factor for acquisition of XDR infection. Conclusion Extensively drug-resistant gram negative infections are frequent in our ICU. This is an alarming health care issue in Egypt which emphasizes the need to rigorously implement infection control practices.


Introduction
Infection due to gram negative bacilli is a growing problem in clinical practice especially in tertiary medical centers. Patients in the intensive care unit (ICU) are highly vulnerable to infections because of impaired host defenses, administration of some drugs e.g. muscle relaxant, and the use of invasive devices that bypass the normal anatomical barriers. The growing emergence of resistant pathogens is considered an additional burden and a major threat to public health [1]. ICU is claimed to be the epicenter and the factory for rising, development and amplification of antimicrobial resistance.
Although, there are currently no internationally accepted definition for the resistant microorganism, the term extensively-drug resistance (XDR) is used to denote isolates resistant to all but one or two classes of antimicrobial agents.
Surveillance studies are not only useful in detection of the prevalence of XDR organisms and taking infection control alarms, but also help determine the special pattern of antibiotic resistance to reach higher rates of initial appropriate therapy as well as saving last-line antibiotic agents [2]. Although some authors reported the prevalence and the burden of nosocomial infections in developing countries in terms of mortality, cost, and length of stay [3]; the data addressing prevalence of XDR is scarce in Egypt, we conducted a prospective cohort study to quantify the incidence, risk factors, and outcome of patients harboring XDR gram negative bacilli in our surgical intensive care unit.

Methods
A one year prospective study was conducted in the Surgical

Data collection
The following data were recorded from all patients with positive results; age, sex, primary diagnosis, APACHE II score, prior antimicrobial therapy within last 3 months, septic shock, repeated The susceptibility of aerobic Gram negative bacteria to 10 antibiotics (cefoperazone, cefotaxime, ceftazidime, cefepime, cefoperazonesulbactam, imipenem, gentamicin, amikacin, colistin and ciprofloxacin) was reported. Extensive drug resistant (XDR) gram negative bacilli were defined as isolates resistant to three or more groups of antimicrobials. Prevalence of XDR isolates was reported among different isolate sites as well as different type of organism.
Patients were further divided into XDR and non XDR groups, both groups were compared as regards possible risk factors as well as outcome.

Statistical analysis
Categorical variables were analyzed using the X2 or Fischer Exact test as appropriate. For continuous variables, the data are presented as median (range) and were analyzed with Mann-Whitney

Risk factors and outcome
Relaparotomy was the only risk factor reported to be associated with increased XDR infections by both univariate and multivariate analysis, all other risk factors included in the study were not significantly associated with acquisition of XDR ( Table 3).

Discussion
The main finding in our study was the high prevalence of XDR gram negative bacilli among all our isolates in all sites; this is similar to the findings of many studies all over the world [4][5][6][7][8][9][10][11][12]. Nosocomial infections carry a high burden in both developed and developing countries, this burden was reported in the terms of mortality, financial losses, and length of stay [1,3]. although some studies reported the prevalence of XDR in Egypt [9][10][11], all of them were usually concerned with only one site of infection such as blood stream infections [9,10] and lower respiratory tract infections [11], and only one study was concerned with critically ill patients in Egypt [9]. Our study described the prevalence of XDR gram negative bacilli in all sites of cultures among critically ill patients in a large teaching hospital.
Some studies reported lower prevalence of XDR than what we found [13,14], this might be because they were conducted in the early 2000s [14] this is supported by the obvious increase of drug resistance year after year all over the world which was reported in few studies [15][16][17][18]. There was a unique exception reported in China by Qin Y et al [19] who described a decrease in XDR isolates, this decrease was explained by the adherence to the principles of antibiotic use and effective monitoring and preventive measures In our study the only significant risk factor for acquisition of XDR infection was relaparotomy while all other classic risk factors were not significantly associated with XDR infections. A similar finding was reported in a recent Belgian multicenter study which showed that some classic risk factors lost their predictive value as in 40% of infected patients with XDR microorganisms [20]. Seguin et al [21] reported a different finding where antimicrobial treatment in the 3 months preceding hospitalization, duration between first operation, and relaparotomy were shown to be independent risk factors for XDR in postoperative peritonitis, also Bayani el al [22]

Prevalence of XDR isolates in our patients was higher in
Pseudomonas and Acinetobacter species than other gram negative bacilli, this is similar to many studies that reported high antimicrobial resistance in these two organisms. Pseudomonas is intrinsically resistant to most antibiotics with multiple mechanisms that are responsible for Antimicrobial resistance such as hyperproduction of enzymes, such as beta-lactamases and DNAgyrases, active efflux pumps, and permeability changes.

Conclusion
In conclusion, extensively drug-resistant gram negative infections are endemic in our ICU. This is an alarming health care issue in Egypt which emphasizes the need to rigorously implement infection control practices.

Competing interests
The authors declare no competing interest.

Authors' contributions
All authors read and agreed to the ?nal version of this manuscript and equally contributed to its content and to the management of the case.