Acinetobacter baumannii is a major cause of hospital acquire infections mainly among patients admitted at intensive care units (ICU) in many hospitals [1], regarding its ability to survive for long periods and could easily spread in hospital environment beside developing resistance to multiple antimicrobial agents leading to serious therapeutic problems [2] [3]. These traits could define its propensity for causing extended outbreaks [2]. Throughout last decades, mortality ranging from 5% in general wards to 54% in intensive care units (ICUs) is associated with A. baumannii infections [3] [4]. Carbapenems have been used as the most appropriate choice for treatment of infections due to MDR strains of A. baumannii. Unfortunately, extensive administration of broad-spectrum cephalosporins and/or carbapenems is a significant risk factor for development of colonization or infection with carbapenemase-producing A. baumannii [2] [5]. CPAB in hospital settings ranged from 2.3% to 67.7% in North Africa and from 9% to 60% in sub-Saharan Africa and the major bla genes were OXA-23-like, OXA-58-like, OXA-48-like, NDM-1 and VIM-2 associated with A. baumannii isolates of hospitalized patient years between (2010-2018) [3] [6]. More alarmingly; there was record of extensive drug resistance A. baumannii with intermediate resistance to colistin. This situation leads to limited options for treatment [7]. The lack of systematically collected data on the Sudan area contributes to a poor understanding of antimicrobial resistance and limits an effective response to the problem. The present study was aimed to investigate frequency of carbapenemase producing A. baumannii strains exhibiting extensive drug-resistant (XDR) profile isolated from ICU patients in two large hospitals at Khartoum city of Sudan.

An emerging rise in the incidence of carbapenemase producing A. baumannii has been increasingly reported worldwide [6] and in Sudan as well [13] [14], leaving behind a significant challenging to treat infections. In our study, for a deeper understanding the molecular mechanisms underlying carbapenem resistance, a collection of accurately characterized 38 A. baumannii clinical isolates was screened for carbapenemase-coding genes by PCR. A total of 57.9% (22/38) A. baumannii isolates were confirmed by molecular amplification (PCR) to be carbapenemase positive in clinical samples recovered from ICU patients with severe infections. Among the source of the isolates in the study, the majority of CPAB were from respiratory specimens (72.7%) followed by tip, blood, central line and bed sore specimens, consistent with other studies [1] [14] [15]. Extensive drug resistant among CPAB infections has become a world-wide contest as this organism is resistant to cephalosporins, Monobactams, aminoglycosides, fluoroquinolones, cephalosporins, carbapenems, and now emergence of colistin resistance in this species is of significant concern, leaving restricted treatment options for ICU infections. In our region, lack of systematically identification of A. baumannii infection among ICU patients and environments in hospital contributes to a poor understanding of antimicrobial resistance and limits an effective response to the problem. In recent years, the global emerge of extensive drug resistant producing carbapenemase A. baumannii, the strains have significantly threatened public health and become a major problem in the intensive care unit (ICU) reported by [1] [4] [16]. The results of the present study show that there was an extreme increase in the resistance rate of A. baumannii to meropenem, from 89% in 2015 to 100% in 2019 [14] [17]. In addition, the resistance rate of A. baumannii to colistin was 60.5%, which is higher than in previous reports in Khartoum state and other studies [1] [4] [13] [14] [16]. The present study showed 100% resistant rates of the most clinically applicable antibiotics for the treatment of infections caused by A. baumannii, except for colistin, which may be used as the final options in the management of infections caused by this bacterium. In this study, the high resistance rate of A. baumannii against carbapenems may indicate the outcome of overuse and misuse of carbapenems in our hospital.

Overall, bla_OXA-51-like genes were the most prevalent subgroup, which is consistent with the view that they are intrinsic to A. baumannii [5] [10] [14] [18]. These genes were detected in 7 of 12 isolates, irrespective of levels of carbapenem susceptibility or resistance, these alleles do not correlate with the level of carbapenem resistance of the host isolate. Thus, resistance to carbapenems cannot be inferred from detection of bla_OXA-51-like alleles. In contrast, alleles encoding OXA-23-like, OXA-24-like and OXA-58-like enzymes were consistently associated with resistance or, at least, with reduced susceptibility. The bla_OXA-23-like carbapenemase-producing A. baumannii is becoming widespread globally in Europe, South America, and Asia [19] [20]. In this study, bla_OXA-48-likewas the most common gene encountered in the study isolates as single carbapenemase encoding gene followed by bla_NDM and bla_GES. Various studies have noted that only bla_GES-type carbapenemase was reported in in an Acinetobacter isolate from Mediterranean countries and Kuwait [21] [22]. bla_OXA-23-like carbapenemase was detected in 6 (15.4%) of the 38 carbapenem-resistant isolates and as in terms of carbapenem non-susceptibility, an alarmingly high rate of 75.0% over 2 years was detected, this high rate is similar to that reported by Perez et al. [19] [23]. This rate, however; is much higher than that reported for other African countries [3] revealing a worrisome situation in this country. Alleles encoding bla_{OXA-24/40-like} enzymes were not detected in any of the A. baumannii ICU strains; these enzymes are reported in Portugal, Spain, Poland, Iran, the United States, Asia and Saudi Arabia [3] [5] [20]. In the current study we report bla_NDM-1- producing A. baumannii strains, in contrast to bla_NDM-1 was mostly carried by Enterobacteriaceae; all the bla_NDM-1-positive A. baumannii isolates, which suggests that this species, which has a robust survival capability, can easily acquire foreign resistance genes such as bla_NDM-1 [1] [14] [24]. The coexisted CP-AB was detected in 12 isolated CRAB with (5/22; 22.7%) bla_NDM and bla_OXA-48-like, followed by (4/22; 18.2%) bla_OXA-51-like and bla_OXA-23-like and only two strains of A. baumannii produced bla_OXA-51,bla_OXA-23-like,bla_OXA-143-likeand bla_NDM-1, coexisted carbapenemase gens surveyed in this study as emergent detection in our region, mainly among ICU patients. As the bla_OXA-143-like gene is frequently found in the Southeast region of Brazil, especially in the state of São Paulo. It is important to note that two new variants of this gene were recently described [12].

Here, we detected an emergent OXA subclass identified in two A. baumannii strains bla_OXA-143-like which reported as High-Risk Clones among XDR A. baumannii, whereas bla_OXA-23, bla_OXA-51, bla_NDM-1 and bla_GES producing in XDR A. baumannii strains were prevalent in the ICU. The coexisted genes (bla_OXA-51andbla_{OXA-23-like and}bla_OXA-51,bla_OXA-23-like,bla_OXA-143and bla_NDM-1) were also associated with increased virulence as compared to other OXAs. Therefore, some infection control measures should be covered and implementation of whale genome sequence (WGS) as advanced molecular characterization of infectious agents could improve both, identification and genetic characterization including resistance profiles, facilitating outbreak investigations and molecular surveillance.

We are grateful to Royal Care International Hospital (RCIH) and National Ribat Hospital (NRH) for providing us the Gram negative coccobacilli isolates from ICU patients to perform this study. This work was partly of Ph.D. project under supervision of Prof. Hassan A. Alaziz and Prof. Elamin. M. Ibrahim, in the Alribat National University (Khartoum, Sudan).

This study was approved by the ethics committee of Alribat National University-Graduate Collage. Bacterial isolates ethics approval and consent were not applicable as samples obtained from Microbiology Laboratory remaining samples and coded by Laboratory ID.

The authors declare no conflicts of interest regarding the publication of this paper.

Ibrahim, S.M., Ibrahim, E.M., Ibrahim, O.A., Hamid, O.M. and Alaziz, H.A. (2022) Molecular Detection of Carbapenemase Genes in Extensive Drug Resistant Acinetobacter baumannii Clinical Isolates from ICU Patients, Khartoum. Open Journal of Medical Microbiology, 12, 38-48. https://doi.org/10.4236/ojmm.2022.121004