Evolution of Antibiotic Resistance in Enterobacter Spp Isolated at the Yaounde University Teaching Hospital from January 2008 to November 2019

Introduction

Since their discovery, antibiotics have been the main drug used in the treatment of bacterial infections, in fact antibiotics have been the main defense in the treatment of bacterial infections. However, bacteria are increasingly subject to resistance mechanisms allowing them to escape the actions of antibiotics [1]. Among these bacteria, Enterobacter species are involved in several nosocomial infections [2, 3]. Antibiotic resistance is a real public health problem in the world. The spread of resistant pathogenic bacteria results from poor hygiene, inappropriate and abusive use of antibiotics in low income countries [4]. Several strains of Enterobacter are resistant to a majority of antibiotics except to Carbapenems and colistin [5]. Enterobacter species have presented resistance to β-lactams, quinolones and aminoglycosides in previous studies [6]. Studies of Gonsu, et al. [7] and Nouetchognou, et al. [8] have also revealed resistant strains of Enterobacter in Cameroon. None of these studies have explored the evolution of antibiotic resistance of Enterobacter species.

The level of antibiotic resistance varies from continent to continent, from country to country and from year to year. It seemed important to conduct a retro-prospective study on the evolution of antibiotic resistance of Enterobacter isolated in Cameroon during twelve years.

Results

Samples were collected on 54 (49.5%) males and 55 (50.5%) females. The age range of [60; 80] years was the most affected with a frequency of 23.9%. Overall 109 strains of Enterobacter were isolated from samples, distributed as follows: Blood (36.7%), pus (25.7%), urine (20, 2%), urinary catheter tips (12, 8%), vaginal secretions (1,8%), eye secretions (1,8%), and catheter tips (0,9%). We identified seven species of Enterobacter including Enterobacter cloacae (54,1%), Enterobacter sakazakii (22%), Enterobacter aerogenes (15,6%), Enterobacter agglomerans (2,8%), Enterobacter cancerogenus (2,8%), Enterobacter gergoviae (1,8%) and Enterobacter amnigenus (0,9%).

Regarding the origin of bacteria, the intensive care unit was the most incriminated (29,8 %) followed by the pediatric unit ( 21,3 %), medicine unit ( 13,8 %), neonatalogy ( 12,8 %), emergency (9,6 %), surgery (9,6 %), gynecology ( 1,1 %), ENT ( 1,1 %) units and external (1,1 %).

Discussion

Of the 109 strains isolated, the rates of Enterobacter infection for the female(50.5%) and the male (49.5%) were almost similar, indeed, sex is considered as a physiological criterion without influence on the infections linked to care [2]. Patients between 60 and 80 yearswere the most affected (23.9%). This result is similar to those reported by previous studies conducted in Shanghai [12] and is due to the weakened immune system. For this study, blood was the most represented specimen (36.7%). This result differs from that found by Gonsu et al. which presented urine as the most represented specimen [7]. This would be due to the fact that the species of the genus Enterobacter are ubiquitous. Enterobacter cloacae was most frequently isolated (54.1%). This result is in agreement with those of several studies highlighting Enterobacter cloacae as the main species of this genus [7, 13]. This study showed that intensive care unit presented the highest frequency of Enterobacter spp (29, 8%).Intensive care unit is known as a unit with several risk factors for infections. The study of Anthony, et al. [14] showed that many risks factors as surgery, urethral catherization, endotracheal intubation exposed patients to infections in this unit.

The study of the antibiotic resistance phenotypes indicated a total resistance to amoxicillin and amoxicillin/ clavulanic acid. Thusjustifying the wild phenotype. Resistance has been observed for cefuroxime (77%), ceftazidine (67%), cefixime (57%) and aztreonam (49%). The high resistance to first generation cephalosporins is due to a mutation in the AmpR repressor gene lead to high levels of AmpC production [15]. These results are slightly low compared to the resistance rate found in the study conducted in Algeria [2]. Low resistance was noted for meropenem (14%), ertapenem (12%) and imipenem (9%). Previous studies presented a very high sensivity to carbapenems in Cameroon [7]. The resistance to carbapenem is due to ESBLs or porine alteration [16]. Resistance was noted to nalidixic acid (42%), Ciprofloxacin (38%) and norfloxacin (36%). These percentages are higher than those found by Gonsu, et al. [7] in 2007, and are similar to those found by Khennouchi [2]. This shows an increase of resistance to quinolones recently. Resistance to quinolones is linked to the modification of the target enzyme or to the acquisitionof qnr-A and qnr-B genes [2, 5]. Enterobacter strains showed low resistance to most aminoglycosides. Gentamicin showed an average resistance of 45%. The resistance to gentamicin could be due to the mutation of genes in Enterobacter spp or to theproduction of an enzyme which inactivates aminoglycosides. Amikacin remains the most effective molecule with 87% of sensitive strains as reported by Boudjema [5]. However, we noted 30% ofresistance to colistin which is a molecule that presented a high activity to Enterobacter. Resistance to this molecule is essentially linked to chromosomal mutations of the various genes leading to the modification of lipopolysaccharide charges which will prevent the attachment of colistin. Recently, colistin plasma genes, mcr-1 and mcr-2 have been described in several species [17]. The peak of resistance between 2018 and 2019 reflect an increase of resistance to the majority of antibiotics. Resistance to antibiotics is a growing fact and for which if nothing is done we will reach to a total resistance to all antibiotics for most bacteria.

Conclusion

This study presented various resistances of Enterobacter species to antibiotics during the last 12 years at the University Teaching Hospital of Yaounde. The cephalosporins were the most affected, but we also noted worrying resistance to many antibiotics. This study shows that many resistance phenotypes are present in Yaounde and antibiotic resistances have increased. These resistances require the establishment of a surveillance strategy in order to better detect and control the spread of multi-resistant strains and to adapt an adequate treatment regimen. It would therefore be important to establish a surveillance strategy in all the ten regions of Cameroon and in others countries to make an appropriate choice of first-line antibiotic therapy.