Introduction

Bacterial infections can compromise the host’s health status, making it necessary to use treatments that help and promote the elimination of the pathogen for the proper recovery of the patient. It is important to mention that the severity of bacterial infections depends on the condition and status of the host, such as age, sex, nutritional status, and the presence of other concomitant pathologies (^{Humphries et al., 2021}). Usually, the first-choice treatment against bacterial infections is antibiotics. However, over time its inappropriate use has stimulated bacteria to develop resistance against these drugs (^{Jernigan et al., 2020})

In addition, it has been estimated that for every 100 thousand habitants, infections with antibiotic-resistant bacteria results in 57.9 deaths in Latin America and the Caribbean, 42.0 deaths in North Africa and the Middle East, and 67.7 deaths in Central Europe, Eastern Europe, and Central Asia (^{Murray et al., 2022}). This problem is associated with both Gram-positive and Gram-negative bacteria; however, the latter is the most common (^{Gupta and Datta, 2019}). In this way, it has been reported that Escherichia coli, Acinetobacter baumannii, Klebsiella pneumoniae, and Pseudomonas aeruginosa, are the main causes of nosocomial infections resistant to antibiotic treatment (^{Rello et al., 2019}).

This bacterial resistance may be due to various defense response mechanisms of the microorganism, which allow them to inactivate drugs through their enzymatic system. It can also occur through the expulsion of the drug by flow pumps or, through the modification of its cell wall, reducing its permeability and avoiding the internalization of antibiotics (^{Breijyeh et al., 2020}). In this regard, the increase in infections caused by resistant bacteria implies greater complications in the health of patients, as well as an increase in medical expenses due to the prolongation of convalescence time (^{Banin et al., 2017}). For this reason, it is important to have case records of bacterial infections and identify which of them showed unusual responses to antibiotic treatment, to understand this problem and propose solutions that allow us to deal with future events. Antimicrobial resistance in countries like Mexico is difficult to address because of the absence of a regulatory body to effectively control the use and sale of antimicrobials, the prescription and self-medication, and the lack of information available on antimicrobial resistance (INSP, 2022). Similarly, more research is required in health centers located particularly in northwest Mexico. In this context, this work aimed to collect records of bacterial infections and determine the prevalence of bacterial resistance to antibiotics in patients treated at the Hospital General del Estado (HGE) in Hermosillo, Sonora from January to August 2016, to showcasing the updated status and, to encourage future investigations for comparative analysis. This study intends to furnish pertinent evidence to prompt the relevant authorities to implement appropriate measures for controlling this issue.

Material and methods

To carry out the study, information was collected from the logs of the microbiology area of the HGE from 2,205 registered biological samples, of which, in some cases, more than one bacterium was isolated, keeping data on bacterial cultures with antibiograms of patients older than 18 years, considering the age-group ranges as follows: 18 - 28 (n = 309), 29 - 39 (n = 323), 40 - 50 (n = 475), 51 - 61 (n = 464), 62 - 72 (n = 373), and > 73 (n = 261) years old. The samples consisted of blood, pharyngeal exudate, expectoration, bronchial secretion, catheter tip, tissue, stools, urine, wounds, and their secretions (samples collected with swabs, and transported in microbiological medium Stuart). These data were obtained from the VITEK® system (Biomeireux), which provided information about the identity of the bacteria, their resistance to antibiotics, type of the antibiotic to which were resistant as well as the capacity to produce extended-spectrum beta-lactamases (ESBL).

Information was classified based on the hospital service area from which the samples came; external consultation (EC), emergency room (ER), infectious diseases (IFN), orthopedics (ORT), surgery for men (SURM), medicine for men (MEDM), intensive therapy unit (ITU), medicine for women (MEDW), intensive care unit (ICU), women’s surgery (SURW) and hemodialysis (HEM). All the information was collected from January to August 2016. The present study was a cross-sectional, and retrospective aimed to determine the bacterial prevalence by species and hospital area, as well as the percentage of bacterial resistance (% R) to each and type of antibiotic by species, age group, sex, and hospital area. This study was evaluated and approved by the ethics committee of the Hospital General del Estado in Hermosillo, Sonora.

A 2-sided Chi-square test was performed on the data obtained to establish differences in antibiotic resistance between females and males. All the data were analyzed with the STATA package version 2012 at a significance level of p ≤ 0.05.

Results

Table 1 shows the bacterial species isolated during the study based on rank of prevalence: E. coli (28.8 %), Staphylococcus aureus (11.5 %), P. aeruginosa (9.8 %), Klebsiella pneumoniae spp. (7.5 %) and Staphylococcus hominis (4.1 %). The hospital area with the highest general prevalence of bacterial species (Table 2) was EC (23.0 %), followed by ER (15.0 %), INF (11.0 %), and ORT (11.0 %). The species with the highest prevalence in EC (48.8 %), ER (38.4 %), SURM (33.0 %), and MEDW (28.6 %) was E. coli.

In addition, Table 3 shows data on bacterial resistance to antibiotics. For Gram-negative bacteria a higher resistance to ampicillin (AMP) (85.2 %), ampicillin/sulbactam (SAM) (68.9 %), and cefazolin (CFZ) (61.0 %) was registered. On the other hand, for Gram-positive bacteria a higher resistance to benzylpenicillin (BPE) (87.6 %), AMP (60.7 %), and erythromycin (ERI) (60.4 %) was also estimated. Furthermore, 37 % of ESBL were positive out of 818 records analyzed.

Table 4 shows the prevalence of bacterial species resistance to commonly used antibiotics by service area out of 1,781 records. As before, for BPE the highest prevalence of resistance in the ER (19.0 %) was observed, followed by IFN (14.7 %), ICU (8.1 %), ITU (7.6 %), and HEM (3.9 %). For AMP, a higher resistance was observed in EC (29.8 %) and SURM (9.7 %); and finally, for cefazolin (CFZ) in ORT (17.3 %). In addition, the highest prevalence of ESBL (15.1 %) was observed in EC.

Regarding the information by age groups (Table 5), E. coli showed the highest prevalence in patients of all ages, followed by S. aureus (10.5 - 13.0 %) and P. aeruginosa (7.1 - 13.0 %). However, patients in the age- range 51- 61 years (n = 148) (data not shown) showed the highest prevalence (31.2 %). BPE was the antibiotic to which a high prevalence of resistance was found in patients between 18 and 61 years old (from 84.1 to 91.7 %). On the other hand, the resistance to AMP was the highest (85.3 %) in patients aged 62 and 72 years. In addition, the highest resistance to ESBL was found in patients between 40 - 50 and 62 - 72 years old (39.8 and 39.5 % respectively).

On the other hand, a higher prevalence of infections was observed in males (n = 1,213) than in females (n = 802), being E. coli the most frequent in both groups (data not shown).

Lastly, the prevalence of resistance by sex is shown in Table 6. High resistance to BPE, AMP, and SAM was found (88.8, 81.4, and 67.3 %, respectively) in isolates from female patients (n = 865). Similarly, in male patients (n = 1,340), the highest resistance was also observed to BPE, AMP, and SAM (86.9, 84.9, and 70.2 %, respectively). Thus, the antibiotics to which a significant difference in bacterial resistance was found between sexes were OXA, CFZ, cefoxitin (CTX), ceftriaxone (CRO), aztreonam (ATM), piperacillin/tazobactam (TZP), ciprofloxacin (CIP), amikacin (AMK), nitrofurantoin (NIT), tigecycline (TGY), and linezolid (LZ). On the other hand, a higher percentage of bacterial resistance was found for each one of the mentioned antibiotics in women than in males. Finally, the prevalence of ESBL in females and males was 33.1 and 41.2 % respectively.

Discussion

Currently, reports are indicating that E. coli, S. aureus, K. pneumoniae and P. aeruginosa, are the main bacteria causing deaths worldwide (^{Murray et al., 2022}), and they were predominant in this study. On the other hand, the Mexican Ministry of Health in 2011 analyzed a total of 48,377 biological samples, and reported E. coli with 16.9 % (8,192 samples) as the most isolated bacteria species, followed by the coagulase-negative Staphylococcus (S. hominis, S. epidermidis, S. saprophyticus, and S. haemolyticus) with 14.0 % (6,771 samples), and P. aeruginosa with 10.9 % (5,275 samples) (^{Arias-Flores et al., 2016})followed by the group of Coagulase-negative Staphylococci with 6771 cultures (14 %, which agreed with this study. It has been reported that in countries such as Ethiopia, E. coli, P. aeruginosa, and K. pneumoniae, are the most common antibiotic resistant-bacteria, suggesting that those bacterial species are the most serious health problem worldwide (^{Berhe et al., 2021}). It is recognized that ESBL-producing E. coli infections are not necessarily considered as an intra-hospital infection since these have already been reported in outpatients. This may explain the high prevalence of infections registered in EC and ER, suggesting that this type of pathogens may be spreading outside hospitals (Rodríguez-Baño et al., 2004).

The findings in this study revealed a high prevalence of bacteria resistant to antibiotics belonging to the beta-lactams group (penicillins and cephalosporins), and to ERI belonging to the macrolides and lincosamides group. In another study carried out in 2017 in 47 health centers and 20 regions of Mexico, a high bacterial resistance to third and fourth-generation cephalosporins (> 50.0 %) and trimethoprim-sulfamethoxazole (> 60.0 %) was reported (^{Garza-González et al., 2019}). In addition, such data is like that of this study (47.1 %). β-lactam antibiotics are the choice treatment and they are effective against some pathogenic bacteria (^{Russ et al., 2020}). Likewise, some bacteria can produce ESBL, enzymes that confer resistance against β-lactam antibiotics. These enzymes hydrolyze the β-lactam ring of the antibiotic limiting its therapeutic activity (^{Hermann et al., 2005}). In agreement to this, an increase in the appearance of bacterial resistant to ceftriaxone, belonging to the group of cephalosporins, has been observed, mainly by E. coli and K. pneumoniae (^{Rolain et al., 2016}). In this regard, these two bacteria are commonly associated with the production of ESBL. E. coli and K. pneumoniae are frequently found in the human intestine and they spread through feces which implies a public health problem (^{Cocker et al., 2022}).

ESBL-producing microorganisms are frequently multi-resistant. So, the SENTRY Antimicrobial Surveillance Program has revealed a prevalence of ESBL-producing E. coli and K. pneumoniae of 45.0 and 8.5 % in Latin America; 7.6 and 3.3 % in the United States; and 22.6 and 5.3 % in Europe. These bacteria cause infections in hospitalized patients with malnutrition and comorbidities, and carbapenems may be the first choice of treatment because they are resistant to hydrolysis by ESBL-producing bacteria (^{Navarro-Navarro et al., 2011}).

A high prevalence of resistance was observed in the ER, IFN and ICU services, with BPE as the antibiotic to which the highest resistance was recorded. It is noteworthy to mention that in the ICU, usually critical state patients with compromised immune systems are accommodated (^{López-Pueyo et al., 2011}). A study conducted in 2012 at the Daniel Alcides National Hospital in Peru analyzed 3,149 samples from patients with intra-hospital infections and reported that 29.4 % were ESBL-producing bacteria, and the area with the highest prevalence was EC with 37.42 % (^{Tejada Llacsa et al., 2015}). On the other hand, a high prevalence of ESBL in people being attended at external consultation, reinforces the idea that this problem goes beyond intra-hospital infections. It has been reported that in the University of Lagos Medical Centre (n = 350), ESLB-producing bacteria (mainly E. coli and K. pneumoniae) resistant to AMP were isolated from stool and urine samples of apparently healthy outpatient (Deji-Agboola et al., 2020). It is evidenced that antibiotic-resistance genes are spreading outside hospitals and many of these bacteria may be part of the human microbiota emphasizing the seriousness of this problem.

On another hand, the most prevalent bacterium in any age group was E. coli, showing the highest prevalence in patients older than 40 years. Previous reports has stated that patients between 60 and 70 years old (Xiamen, China, 2015) suffer infections associated with antibiotic-resistant A. baumannii (^{Huang et al., 2018}). It has suggested that adult patients might be more susceptible to some bacterial infections than younger patients. The literature has reported that older people may be more susceptible to different pathologies, due to natural physiological changes that may influence the immune system status (^{Sadighi Akha, 2018}).

In this study, a trend of higher prevalence of antibiotic-resistant bacteria was observed with age, which may be an important criterion regarding the sensitivity of some antibiotics. It has been proposed that resistance is more frequent in people over 60 years old in comparison to younger ones, probably associated with the frequent use of catheters and a high occurrence of chronic diseases (^{Zúniga-Moya et al., 2016}). Furthermore, a study of 3,149 participants showed that the age group with the highest prevalence of ESBL-producing bacteria was over 65 years old (26.6 %) (^{Tejada Llacsa et al., 2015}). However, the high prevalence of resistance to the penicillin group (> 80 %) isolated from all age groups, has suggested that penicillins are no longer effective (^{Marín and Gudiol, 2003}).

On the other hand, a higher number of infections were observed in men as compared to women. It has been reported that, in mammals, males can become more susceptible to infections than females, an event probably associated with variations in the immune response dependent by sex (^{Klein and Flanagan, 2016}). Cases of infections by pathogenic bacteria are more frequent in male than in female. It has been thought that women may have a better immune defense due to an increased response by some cells of the innate immune system (macrophages and dendritic cells) reducing the risk of infection (^{vom Steeg and Klein, 2016}).

On the other hand, sex hormones levels may also play an important role in the function of some immune cells (lymphocytes, macrophages, and dendritic cells). The interaction of sex hormones with some receptors can directly influence signaling processes associated with the production of cytokines, which can vary depending on sex (^{Kadel and Kovats, 2018}). However, this remains unclear. It has also been observed that the presence of ESBL is dependent on age and sex, and is more commonly observed in elderly people and males, so actions should be proposed to attend to the most vulnerable groups (^{Martin et al., 2016}).

Currently, the bacterial resistance to antibiotics shows a high variability worldwide. Apparently, the developed countries have shown a lower incidence of this health problem than in some African and Latin-American countries (^{Health Policy Watch, 2022}). For example, in Mexico, a few studies carried out at different hospitals reported a high prevalence of bacterial resistance and it remains unchanged with time, while this problem tends to increase in other countries. This has suggested that strategies to curb this situation in some countries have been somehow established without being monitored, while in others they are urgently required (^{Patel et al., 2023}).

Additionally, it is important to consider that the severity of this problem may be greater, because since the 2019 to March 2020 period of the SARS-COV-2 pandemic, an increase of 11.2 % in the consumption of antimicrobials was registered worldwide (^{Khouja et al., 2022}). In Mexico, an increase was also recorded in bacterial resistance during this pandemic, with predominant cases of S. aureus resistant to OXA, and K. pneumoniae resistant to carbapenem (data from 46 centers in Mexico) (^{López-Jácome et al., 2022}). In addition, other studies carried out in Northwestern Mexico have suggested that a third of the population resorted self-medication due to the pandemic, however, drugs used were not identified (^{Torres Soto et al., 2022}). This situation can change the current context of resistance in this region, so new studies are required to follow up on this problem in the city of Hermosillo, to take actions in real time to prevent a more serious stage.

Conclusions

Updated information about the prevalence of bacterial species that cause infections in patients of different hospital areas, will allow for the design of hospital prevention and control strategies for E. coli, S. aureus, P. aeruginosa, K. pneumoniae spp, S. haemolyticus, and S. hominis infections, which are commonly isolated from biological samples collected from HGE patients during the study period. On the other hand, the use of antibiotics in hospital patients should be monitored based on their route of administration, dose, treatment extension, and interactions with other medications. Also, special attention should be paid to the management of antibiotics belonging to the β-lactams, as they are the antibiotics against which the highest resistance was found. In addition, it is advisable to monitor the patient effectively complies with his treatment period, to prevent the increase of bacterial resistance and the appearance of multi-resistant strains as evidenced by this work.

Conflicts of interest

The authors declare no conflict of interest.