Journal of biological and health sciences http://biotecnia.unison.mx
ISSN: 1665-1456
Estatus de la resistencia bacteriana en un hospital de nivel 2 en el noroeste de México en 2016
1 Centro de Investigación en Alimentación y Desarrollo, A.C. (CIAD, AC). Departamento de Nutrición Pública y Salud, Sonora, Hermosillo, México.
2 Departamento de Ciencias Químico Biológicas, Universidad de Sonora, Hermosillo, México.
3 Departamento de Ciencias de la Salud, Universidad de Sonora, Cd. Obregón, Sonora, México.
4 Laboratorio clínico del Hospital General del Estado, Sonora, Hermosillo, México.
Bacterial infections can be serious and require antibiotic treatment. However, the overuse of antibiotics has led to the development of antibacterial resistance, which can make infections more dangerous. This is a serious problem in Mexico, where published research on antibiotic resistance is limited. This study aimed to estimate the prevalence of antibiotic resistance in bacterial infections at the Hospital General del Estado in Hermosillo (HGE), Mexico so that it can be compared with future information and look for strategies to mitigate this problem. Information was collected from logs registered at the hospital microbiology area in 2016, on bacterial cultures with antibiograms from 2,205 biological samples. These data were obtained from the VITEK® system, which provided information on the bacteria spp., their anti- biotic resistance, and the type of antibiotics to which were resistant. Escherichia coli (28.8 %), Staphylococcus aureus (11.5
%), and Pseudomonas aeruginosa (9.8 %) were the most isola- ted bacteria. The highest prevalence of resistance was found against beta-lactam antibiotics. This study revealed that antibiotic resistance is a serious problem at the HGE. These findings highlight the need for further research on antibiotic resistance in Mexico to design national prevention strategies. Keywords: Bacterial resistance, Antibiotics, Bacterial infec- tions, Northwest Mexico
Cuando las infecciones bacterianas son serias requieren anti- bióticos como tratamiento de elección. Sin embargo, su uso excesivo ha conducido al desarrollo de bacterias resistentes, haciéndolas más peligrosas. Este es un serio problema de salud en México, donde la publicación de investigación sobre este tópico es aún limitada. Este estudio tuvo como objetivo estimar la prevalencia de resistencia a los antibióticos en infecciones bacterianas en el Hospital General del Estado en Hermosillo (HGE), México, y comparase con información futura, estimar tendencias, y buscar estrategias contra este
*Correspondence author: Luis Quihui Cota e-mail: lquihui@ciad.mx
problema. Se recopiló información de 2,205 registros micro- biológicos sobre cultivos bacterianos con antibiogramas de muestras de pacientes en 2016. Estos datos se obtuvieron a través del sistema VITEK®, que proporcionó información sobre las especies bacterianas, y su resistencia contra y tipo de antibióticos. Las bacterias más aisladas fueron Escherichia coli (28.8 %), Staphylococcus aureus (11.5 %) y Pseudomonas aeruginosa (9.8 %). Las prevalencias más altas de resistencia se encontraron contra antibióticos beta-lactámicos. La resis- tencia a los antibióticos es un problema grave de salud en el HGE. Esto resalta la necesidad de investigar más sobre la resistencia a los antibióticos en México, para que las autori- dades consideren tal información en el diseño de estrategias preventivas.
ciones bacterianas, Noroeste de México
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 infec- tions 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 Ca- ribbean, 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, Acineto-
Volume XXV, Issue 3
bacter 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 coun- tries 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 con- text, this work aimed to collect records of bacterial infections and determine the prevalence of bacterial resistance to anti- biotics 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.
To carry out the study, information was collected from the logs of the microbiology area of the HGE from 2,205 registe- red biological samples, of which, in some cases, more than one bacterium was isolated, keeping data on bacterial cul- tures with antibiograms of patients older than 18 years, con- sidering 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 consis- ted 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 infor- mation 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), ortho- pedics (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 bacte- rial 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 bet- ween females and males. All the data were analyzed with the STATA package version 2012 at a significance level of p ≤ 0.05.
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 prevalen- ce 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 ben- zylpenicillin (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 resis- tance 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).
Table 1. Prevalence of bacterial species isolated and identified from 2,205 biological samples at the Hospital General del Estado in Hermosillo, Sonora, during the January to August 2016 period.
Tabla 1. Prevalencia de especies bacterianas aisladas e identificadas de 2,205 muestras biológicas en el Hospital General del Estado en Hermosillo, Sonora, durante el período de enero a agosto de 2016.
Gram positive bacteria | Gram negative bacteria | ||
Bacterial species | Prevalence n (%) | Bacteria species | Prevalence n (%) |
Staphylococcus aureus | 254 (11.5 %) | Escherichia coli | 634 (28.8 %) |
Staphylococcus hominis spp. hominis | 90 (4.1 %) | Pseudomonas aeruginosa | 215 (9.8 %) |
Enterococcus faecalis | 84 (3.8 %) | Klebsiella pneumoniae spp. pneumoniae | 166 (7.5 %) |
Staphylococcus epidermidis | 73 (3.3 %) | Enterobacter cloacae spp. cloacae | 83 (3.8 %) |
Streptococcus mitis | 28 (1.3 %) | Proteus mirabilis | 77 (3.5 %) |
Streptococcus parasanguinis | 27 (1.2 %) | Acinetobacter baumannii | 64 (2.9 %) |
Streptococcus pneumoniae | 21 (0.95 %) | Citrobacter freundii | 30 (1.4 %) |
Staphylococcus lentus | 15 (0.7 %) | Stenotrophomonas maltophilia | 26 (1.2 %) |
Enterococcus faecium | 13 (0.6 %) | Morganella morganii spp. morganii | 21 (0.9 %) |
Kocuria kristinae | 13 (0.6 %) | Klebsiella oxytoca | 18 (0.8 %) |
Staphylococcus intermedius | 10 (0.5 %) | Klebsiella aerogenes | 12 (0.5 %) |
Staphylococcus warneri | 10 (0.5 %) | Serratia marcescens | 12 (0.5 %) |
Streptococcus sanguinis | 7 (0.31 %) | Enterobacter cloacae complex | 10 (0.5 %) |
Staphylococcus sciuri | 6 (0.3 %) | Acinetobacter baumannii complex | 8 (0.4 %) |
Kocuria rosea | 6 (0.3 %) | Providencia rettgeri | 7 (0.3 %) |
Enterococcus gallinarum | 5 (0.2 %) | Raoultella ornithinolytica | 7 (0.3 %) |
Aerococcus viridans | 4 (0.2 %) | Pseudomonas luteola | 6 (0.3 %) |
Staphylococcus haemolyticus | 4 (0.2 %) | Enterobacter cloacae spp. dissolvens | 5 (0.2 %) |
Escherichia coli | 634 (28.8 %) | Aeromonas hydrophila | 5 (0.2 %) |
Pseudomonas aeruginosa | 215 (9.8 %) | Providencia stuartii | 4 (0.2 %) |
Klebsiella pneumoniae spp. pneumoniae | 166 (7.5 %) | Burkholderia cepacia | 4 (0.2 %) |
Acinetobacter haemolyticus | 4 (0.2 %) | ||
Achromobacter xylosoxidans | 3 (0.1 %) |
n = number of bacterial isolates.
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), ceftria- xone (CRO), aztreonam (ATM), piperacillin/tazobactam (TZP), ciprofloxacin (CIP), amikacin (AMK), nitrofurantoin (NIT), tige- cycline (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.
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 predo- minant in this study. On the other hand, the Mexican Ministry of Health in 2011 analyzed a total of 48,377 biological sam- ples, 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. sapro- phyticus, 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
Table 2. Prevalence of bacterial species isolated and identified from 2,113 biological samples by care services at the Hospital General del Estado in Hermosillo, Sonora, from January to August 2016.
Tabla 2. Prevalencia de especies bacterianas aisladas e identificadas a partir de 2,113 muestras biológicas por servicios de atención del Hospital General del Estado en Hermosillo, Sonora, durante el período de enero a agosto de 2016.
Bacterial species | EC (%) | ER (%) | INF (%) | ORT (%) | SURM (%) | MEDM (%) | ITU (%) | MEDW (%) | ICU (%) | SURW (%) | HEM (%) |
E. coli | 48.8 | 38.4 | 12.8 | 19.3 | 23.6 | 15.8 | 13.3 | 28.6 | 7.5 | 33.0 | 11.3 |
S. aureus | 4.3 | 15.0 | 9.0 | 22.3 | 13.3 | 8.9 | 15.6 | 7.6 | 15.0 | 7.4 | 15.9 |
P. aeruginosa | 7.2 | 4.2 | 8.5 | 12.0 | 12.0 | 10.8 | 12.0 | 5.0 | 19.6 | 18.0 | 2.3 |
K. pneumoniae | 8.4 | 6.6 | 8.1 | 4.3 | 8.7 | 7.6 | 12.0 | 5.9 | 3.7 | 9.6 | 2.3 |
S. haemolyticus | 2.0 | 2.7 | 12.0 | 1.7 | 5.6 | 12.0 | 6.3 | 13.4 | 6.5 | 2.1 | 4.5 |
S. homini | 1.6 | 4.8 | 6.4 | 4.3 | 2.1 | 7.0 | 3.1 | 5.9 | 7.5 | 1.1 | 9.1 |
E. faecalis | 3.7 | 5.4 | 3.0 | 3.4 | 4.6 | 3.8 | 3.9 | 3.4 | 0.0 | 3.2 | 0.0 |
E. cloacae spp. cloacae | 2.7 | 3.0 | 5.6 | 8.2 | 1.5 | 3.8 | 2.3 | 3.4 | 1.9 | 3.2 | 18.2 |
P. mirabilis | 3.3 | 3.9 | 1.3 | 3.9 | 7.2 | 2.5 | 4.7 | 2.5 | 0.9 | 3.2 | 2.3 |
S. epidermidis | 1.4 | 2.1 | 3.0 | 2.6 | 3.6 | 2.5 | 5.5 | 4.2 | 0.0 | 4.3 | 0.0 |
A. baumannii | 1.2 | 0.3 | 5.1 | 3.0 | 3.1 | 6.3 | 4.7 | 2.5 | 9.3 | 2.1 | 0.0 |
C. freundii | 1.0 | 0.6 | 3.8 | 1.3 | 1.5 | 1.9 | 0.8 | 1.7 | 0.0 | 0.0 | 0.0 |
S. mitis | 1.2 | 1.2 | 3.4 | 0.9 | 0.5 | 1.3 | 0.8 | 1.7 | 0.9 | 1.1 | 2.3 |
S. parasanguinis | 2.3 | 0.3 | 3.0 | 0.4 | 0.0 | 1.3 | 0.8 | 2.5 | 0.0 | 0.0 | 2.3 |
S. maltophilia | 0.2 | 1.2 | 4.3 | 0.4 | 0.5 | 1.3 | 0.8 | 0.0 | 3.7 | 1.1 | 0.0 |
M. morganii | 1.8 | 0.9 | 0.4 | 0.4 | 1.0 | 2.5 | 0.0 | 0.8 | 0.0 | 0.0 | 2.3 |
S. pneumoniae | 1.2 | 0.9 | 0.9 | 0.0 | 0.0 | 1.3 | 2.3 | 0.8 | 3.7 | 0.0 | 0.0 |
K. oxytoca | 0.4 | 1.2 | 0.4 | 0.0 | 1.0 | 1.3 | 1.6 | 0.0 | 0.0 | 3.2 | 2.3 |
S. lentus | 1.0 | 0.6 | 0.4 | 1.7 | 0.0 | 1.3 | 0.0 | 0.0 | 0.9 | 0.0 | 0.0 |
E. faecium | 0.0 | 0.9 | 0.9 | 0.0 | 1.0 | 1.3 | 0.0 | 0.0 | 0.9 | 2.1 | 0.0 |
K. kristinae | 0.2 | 0.3 | 0.4 | 0.4 | 0.5 | 0.6 | 0.8 | 2.5 | 1.9 | 1.1 | 0.0 |
K. aerogenes | 0.2 | 0.0 | 0.4 | 0.0 | 1.5 | 1.3 | 1.6 | 1.7 | 1.9 | 0.0 | 0.0 |
S. marcescens | 1.6 | 0.6 | 0.0 | 0.0 | 0.0 | 0.6 | 0.0 | 0.8 | 0.0 | 0.0 | 0.0 |
E. cloacae spp. complex | 0.4 | 0.9 | 0.4 | 0.9 | 0.5 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 |
S. intermedius | 0.8 | 0.0 | 0.9 | 0.4 | 0.0 | 0.6 | 1.6 | 0.8 | 0.0 | 0.0 | 0.0 |
S. warneri | 0.0 | 0.0 | 1.3 | 2.1 | 0.5 | 0.0 | 0.0 | 0.0 | 0.9 | 0.0 | 0.0 |
A. baumannii complex | 0.0 | 0.0 | 1.3 | 0.9 | 0.0 | 0.0 | 0.8 | 1.7 | 0.0 | 0.0 | 0.0 |
P. rettgeri | 0.4 | 0.3 | 0.0 | 0.0 | 0.5 | 0.6 | 0.8 | 0.8 | 0.0 | 0.0 | 0.0 |
R. ornithinolytica | 0.6 | 0.0 | 0.4 | 0.9 | 0.5 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 |
S. sanguinis | 0.6 | 0.0 | 0.0 | 0.0 | 1.5 | 0.0 | 0.0 | 0.0 | 0.9 | 0.0 | 0.0 |
TOTAL (n) | 512 | 333 | 237 | 233 | 201 | 158 | 128 | 119 | 107 | 88 | 44 |
23 % | 15 % | 11 % | 11 % | 9 % | 7 % | 6 % | 5 % | 5 % | 4 % | 2 % |
EC= external consultation; ER= emergency room; INF= infectious diseases; ORT= orthopedics; SURM= surgery for man; MEDM= medicine for man; ITU= intensive therapy unit; MEDW= medicine for women; ICU= intensive care unit; SURW= surgery for women; HEM= hemodialysis.
Table 3. Prevalence of resistance (% R) of the bacterial species isolated and identified from 2,205 biological samples against the antibiotics used at the Hospital General del Estado in Hermosillo, Sonora, from January to August 2016.
Tabla 3. Prevalencia de resistencia (% R) de las especies bacterianas aisladas e identificadas de 2,205 muestras biológicas frente a los antibióticos utilizados en el Hospital General del Estado en Hermosillo, Sonora, de enero a agosto de 2016.
Drugs | Gram negative bacteria | Gram positive bacteria | |
Drug group | Antibiotic | % R | % R |
I Beta-lactams | |||
AMP | 85.23 | 60.7 | |
1. Penicillins | BPE | ND | 87.61 |
OXA | ND | 54.51 | |
CFZ | 61.05 | ND | |
2. Cephalosporins | FEP | 37.37 | ND |
CTX | ND | 42.18 | |
CRO | 48.02 | ND | |
3. Monobactam | ATM | 38.91 | ND |
4. Beta-lactam/beta-lactamase inhibitors | SAM | 68.94 | ND |
TZP | 30.75 | ND | |
5. Carbapenems | ETP | 2.47 | ND |
MEM | 11.06 | ND | |
CIP | 47.02 | 45.93 | |
II Quinolones | LVX | ND | 42.92 |
MFX | ND | 31.26 | |
AMK | 8.9 | ND | |
STR | ND | 34.31 | |
III Aminoglycosides | |||
GEN | 29.79 | 21.12 | |
TOB | 33.9 | ND | |
SXT | 54.46 | 28.86 | |
IV Sulfonamide/Trimethoprim | |||
NIT | 46.02 | 4.57 | |
CLI | ND | 58.7 | |
V Macrolides and Lincosamides | |||
ERI | ND | 60.47 | |
TCY | ND | 24.26 | |
VI Tetracyclines/Glycylcyclines | |||
TGY | 28.33 | 1.48 | |
LZ | ND | 0.87 | |
VII Oxazolidone and streptogramin | |||
QXD | ND | 14.49 | |
VIII Rifamycins | RIF | ND | 14.26 |
IX Glycopeptides | VAN | ND | 0.88 |
ESBL | NEG* 516 (63 %) | POS* 302 (37 %) | |
*POS= positive y NEG= negative. Ampicillin (AMP); benzylpenicillin (BPE); oxacillin (OXA); cefazolin (CFZ); cefepime (FEP); cefoxitin (CTX); ceftriaxone (CRO); aztreonam (ATM); ampicillin sulbactam (SAM); piperacillin/tazobactam (TZP); ertapenem (ETP); meropenem (MEM); ciprofloxacin (CIP); levofloxacin (LVX); moxifloxacin (MFX); amikacin (AMK); streptomycin (STR); gentamicin (GEN); tobramycin (TOB); trimethoprim+sulfamethoxazole (SXT); nitrofurantoin (NIT); clindamycin (CLI); erythromycin (ERI); tetracycline (TCY); tigecycline (TGY); linezolid (LZ); quinupristin/dalfopristin (QXD); rifampicin (RIF); vancomycin (VAN); ESBL= extended-spectrum beta-lactamases.
Table 4. Prevalence of resistance (% R) of bacterial species isolated and identified from 1,781 biological samples from different care areas at the Hospital General del Estado in Hermosillo, Sonora, during the January to August 2016 period.
Tabla 4. Prevalencia de resistencia (% R) que presentan las especies bacterianas aisladas e identificadas de 1,781 muestras biológicas en las diferentes áreas de atención del Hospital General del Estado en Hermosillo, Sonora, durante el período de enero a agosto de 2016.
*TX | ORT | SURM | HEM | INF | ITU | EC | ICU | ER |
% R | % R | % R | % R | % R | % R | % R | % R | |
AMP | 9.0 | 9.7 | 0.8 | 8.9 | 5.5 | 29.8 | 4.0 | 15.0 |
BPE | 14.5 | 9.2 | 3.9 | 14.7 | 7.6 | 10.1 | 8.1 | 19.0 |
OXA | 6.5 | 6.1 | 2.4 | 12.8 | 3.7 | 5.4 | 6.1 | 8.2 |
CFZ | 17.3 | 9.6 | 2.5 | 3.5 | 4.4 | 2.0 | 0.7 | 0.3 |
FEP | 4.4 | 3.0 | 0.2 | 3.4 | 2.5 | 22.3 | 1.1 | 4.4 |
CTX | 7.5 | 6.8 | 0.9 | 13.2 | 4.9 | 5.3 | 6.2 | 9.3 |
CRO | 7.3 | 5.7 | 0.3 | 6.5 | 3.9 | 13.4 | 3.3 | 6.5 |
ATM | 5.4 | 3.8 | 0.3 | 5.6 | 2.9 | 12.0 | 1.7 | 6.2 |
SAM | 7.3 | 7.0 | 0.7 | 6.1 | 3.9 | 29.6 | 3.4 | 11.0 |
TZP | 7.7 | 3.2 | 0.5 | 5.3 | 4.0 | 3.2 | 2.4 | 3.4 |
ETP | 0.2 | 0.1 | 0.0 | 0.1 | 0.2 | 0.6 | 0.0 | 1.1 |
MEM | 1.6 | 1.5 | 0.0 | 0.7 | 1.2 | 2.5 | 1.2 | 1.2 |
CIP | 6.0 | 4.6 | 1.0 | 6.4 | 3.0 | 14.4 | 2.7 | 7.6 |
LVX | 5.0 | 5.3 | 1.8 | 9.9 | 2.8 | 3.5 | 4.2 | 7.4 |
MFX | 4.0 | 4.6 | 1.1 | 6.8 | 2.2 | 2.6 | 2.4 | 6.2 |
AMK | 4.0 | 4.6 | 1.1 | 6.8 | 2.2 | 2.6 | 2.4 | 6.2 |
STR | 3.6 | 2.4 | 0.0 | 7.1 | 1.2 | 8.3 | 1.2 | 9.5 |
GEN | 4.1 | 2.4 | 0.4 | 3.7 | 1.9 | 7.2 | 1.6 | 4.8 |
TOB | 5.0 | 2.8 | 0.4 | 3.4 | 2.2 | 12.8 | 1.7 | 5.0 |
SXT | 5.7 | 5.3 | 1.0 | 6.3 | 3.3 | 14.3 | 3.1 | 7.2 |
NIT | 4.2 | 4.3 | 0.2 | 4.0 | 2.7 | 10.1 | 2.4 | 4.4 |
CLI | 7.5 | 7.7 | 2.4 | 12.3 | 5.0 | 7.0 | 4.6 | 10.8 |
ERI | 7.6 | 7.4 | 2.2 | 13.3 | 4.2 | 6.8 | 5.5 | 11.6 |
TCY | 1.5 | 3.1 | 0.9 | 3.5 | 2.0 | 5.4 | 1.5 | 5.0 |
TGY | 3.5 | 2.9 | 0.2 | 2.3 | 1.5 | 5.1 | 1.3 | 2.6 |
LZ | 0.0 | 0.2 | 0.0 | 0.2 | 0.0 | 0.0 | 0.0 | 0.2 |
QXD | 1.7 | 2.4 | 0.2 | 1.7 | 1.1 | 3.1 | 0.6 | 3.7 |
RIF | 1.3 | 0.6 | 0.4 | 6.5 | 0.9 | 1.1 | 1.1 | 1.7 |
VAN | 0.0 | 0.2 | 0.0 | 0.0 | 0.4 | 0.0 | 0.0 | 0.2 |
ESBL | 3.6 % | 3.0 % | 0.3 % | 3.9 % | 2.2 % | 15.1 % | 0.6 % | 7.0 % |
TX= antibiotic, ampicillin (AMP); benzylpenicillin (BPE); oxacillin (OXA); cefazolin (CFZ); cefepime (FEP); cefoxitin (CTX); ceftriaxone (CRO); aztreonam (ATM); ampicillin sulbactam (SAM); piperacillin/tazobactam (TZP); ertapenem (ETP); meropenem (MEM); ciprofloxacin (CIP); levofloxacin (LVX); moxifloxacin (MFX); amikacin (AMK); streptomycin (STR); gentamicin (GEN); tobramycin (TOB); trimethoprim+sulfamethoxazole (SXT); nitrofurantoin (NIT); clindamycin (CLI); erythromycin (ERI); tetracycline (TCY); tigecycline (TGY); linezolid (LZ); quinupristin/ dalfopristin (QXD); rifampicin (RIF); vancomycin (VAN); extended-spectrum beta- lactamases (ESBL); orthopedics (ORT); surgery for man (SURM); hemodialysis (HEM); infectious disease (INF); intensive unit therapy (ITU); external consultation (EC); intensive care unit (ICU); emergency room (ER).
Table 5. Prevalence of resistance (% R) and sensitivity (% S) by age group (years), of bacterial species isolated at the Hospital General del Estado in Hermosillo, Sonora, during the January to August 2016 period, from 2,205 biological samples.
Tabla 5. Prevalencia de resistencia (% R) y sensibilidad (% S) de especies bacterianas aisladas por grupo de edad (años) en el Hospital General del Estado en Hermosillo, Sonora, durante el periodo de enero a agosto de 2016, a partir de 2,205 muestras biológicas.
Antibiotic | (18 - 28) % R | (29 - 39) % R | (40 - 50) % R | (51 - 61) % R | (62 - 72) % R | (>73) % R |
AMP | 70.6 | 80.4 | 83.2 | 80.0 | 85.3 | 78.0 |
BPE OXA CFZ | 91.7 49.5 67.3 | 84.1 50.0 62.6 | 89.9 55.7 64.6 | 85.4 52.8 62.2 | 85.1 60.5 57.1 | 90.3 66.7 51.6 |
FEP | 30.5 | 23.7 | 37.1 | 34.2 | 30.6 | 30.9 |
CTX | 56.1 | 51.8 | 60.7 | 55.6 | 63.2 | 66.7 |
CRO | 54.4 | 42.4 | 48.6 | 49.7 | 44.0 | 41.7 |
ATM | 39.8 | 33.8 | 43.2 | 41.0 | 38.1 | 34.9 |
SAM | 75.7 | 68.2 | 66.5 | 73.6 | 67.9 | 60.5 |
TZP | 44.3 | 17.6 | 38.2 | 27.9 | 24.3 | 34.0 |
ETP | 1.9 | 0.8 | 0.4 | 2.2 | 3.5 | 2.5 |
MEM | 14.6 | 11.9 | 13.5 | 12.1 | 7.1 | 7.7 |
CIP | 41.6 | 35.8 | 48.6 | 49.5 | 50.3 | 52.8 |
LVX | 39.2 | 33.3 | 44.2 | 43.8 | 50.0 | 53.2 |
MFX | 30.0 | 19.8 | 31.9 | 34.3 | 36.2 | 40.3 |
AMK | 13.9 | 6.9 | 12.3 | 10.2 | 4.3 | 5.5 |
STR | 15.4 | 16.7 | 33.3 | 34.5 | 42.1 | 57.1 |
GEN | 23.7 | 22.0 | 28.2 | 27.5 | 31.0 | 28.0 |
TOB | 30.4 | 27.6 | 30.1 | 39.7 | 38.5 | 31.4 |
SXT | 49.5 | 38.3 | 44.4 | 51.8 | 48.4 | 60.6 |
NIT | 33.0 | 27.9 | 30.4 | 32.3 | 35.3 | 36.4 |
CLI | 57.9 | 54.8 | 59.4 | 59.1 | 56.4 | 67.7 |
ERI | 61.0 | 54.0 | 59.4 | 59.9 | 64.9 | 66.1 |
TCY | 11.0 | 13.5 | 30.9 | 30.7 | 30.9 | 32.3 |
TGY | 21.4 | 16.9 | 20.3 | 19.9 | 22.8 | 19.7 |
LZ | 0.0 | 0.0 | 0.0 | 1.9 | 1.3 | 2.1 |
QXD | 13.4 | 10.3 | 10.2 | 18.4 | 19.1 | 16.1 |
RIF | 12.3 | 14.9 | 9.8 | 27.9 | 14.5 | 14.6 |
VAN | 0.0 | 0.8 | 0.0 | 0.7 | 3.2 | 1.6 |
ESBL | ||||||
Ampicillin (AMP); benzylpenicillin (BPE); oxacillin (OXA); cefazolin (CFZ); cefepime (FEP); cefoxitin (CTX); ceftriaxone (CRO); aztreonam (ATM); ampicillin sulbactam (SAM); piperacillin/tazobactam (TZP); ertapenem (ETP); meropenem (MEM); ciprofloxacin (CIP); levofloxacin (LVX); moxifloxacin (MFX); amikacin (AMK); streptomycin (STR); gentamicin (GEN); tobramycin (TOB); trimethoprim+sulfamethoxazole (SXT); nitrofurantoin (NIT); clindamycin (CLI); erythromycin (ERI); tetracycline (TCY); tigecycline (TGY); linezolid (LZ); quinupristin/ dalfopristin (QXD); rifampicin (RIF); vancomycin (VAN); ESBL= extended-spectrum beta-lactamases.
Table 6. Prevalence of resistance (% R) of bacterial species isolated and identified from 865 female patients and 1,340 male patients at the Hospital General del Estado in Hermosillo, Sonora, during the January to August 2016 period.
Tabla 6. Prevalencia de resistencia (% R) de especies bacterianas aisladas e identificadas de 865 pacientes del sexo femenino y 1,340 del sexo masculino en el Hospital General del Estado en Hermosillo, Sonora, durante el período de enero a agosto de 2016.
Drug group | Antibiotic | Female n (% R) | Male n (% R) | p |
I Beta-lactams | ||||
AMP | 490 (81.4) | 632 (84.9) | 0.071 | |
1. Penicillins | BPE | 191 (88.8) | 398 (86.9) | 0.478 |
OXA | 107 (61.1) | 207 (51.6) | 0.034* | |
CFZ | 318 (53.2) | 533 (66.9) | 0.001* | |
FEP | 186 (31.1) | 267 (33.5) | 0.335 | |
2. Cephalosporins | ||||
CTX | 11 (63.4) | 222 (55.4) | 0.001* | |
CRO | 257 (43.1) | 413 (51.9) | 0.001* | |
3. Monobactam | ATM | 186 (35.4) | 273 (42) | 0.021* |
4. Beta-lactam/beta-lactamase inhibitors | SAM | 378 (67.3) | 479 (70.2) | 0.259 |
TZP | 33 (15.7) | 105 (32.8) | 0.001* | |
5. Carbapenems | ETP | 14 (2.8) | 13 (2.2) | 0.497 |
MEM | 50 (8.8) | 95 (12.7) | 0.225 | |
CIP | 338 (47.7) | 579 (46.1) | 0.045* | |
II Quinolones | LVX | 101 (47) | 190 (41) | 0.146 |
MFX | 74 (34.3) | 138 (29.8) | 0.243 | |
AMK | 34 (5.9) | 85 (11.3) | 0.001* | |
STR | 137 (33.8) | 22 (35.5) | 0.798 | |
III Aminoglycosides | ||||
GEN | 227 (27.9) | 330 (26.2) | 0.203 | |
TOB | 197 (32.9) | 279 (34.2) | 0.402 | |
SXT | 385 (49.6) | 554 (45.5) | 0.071 | |
IV Sulfonamide/Trimethoprim | ||||
NIT | 236 (29) | 436 (34.6) | 0.007* | |
CLI | 129 (60) | 269 (58.1) | 0.640 | |
V Macrolides and Lincosamides | ||||
ERI | 137 (63.7) | 273 (59) | 0.238 | |
TCY | 51 (23.8) | 114 (24.6) | 0.824 | |
VI Tetracyclines/Glycylcyclines | ||||
TGY | 127 (15.7) | 274 (21.8) | 0.001* | |
LZ | 2 (1.1) | 3 (0.8) | 0.001* | |
VII Oxazolidone and streptogramin | ||||
QXD | 33 (15.3) | 65 (14.1) | 0.667 | |
VIII Rifamycins | RIF | 28 (16) | 54 (13.5) | 0.430 |
*Chi-square, significance at level of p ≤ 0.05. Ampicillin (AMP); benzylpenicillin (BPE); oxacillin (OXA); cefazolin (CFZ); cefepime (FEP); cefoxitin (CTX); ceftriaxone (CRO); aztreonam (ATM); ampicillin sulbactam (SAM); piperacillin/tazobactam (TZP); ertapenem (ETP); meropenem (MEM); ciprofloxacin (CIP); levofloxacin (LVX); moxifloxacin (MFX); amikacin (AMK); streptomycin (STR); gentamicin (GEN); tobramycin (TOB); trimethoprim+sulfamethoxazole (SXT); nitrofurantoin (NIT); clindamycin (CLI); erythromycin (ERI); tetracycline (TCY); tigecycline (TGY); linezolid (LZ); quinupristin/ dalfopristin (QXD); rifampicin (RIF); vancomycin (VAN); ESBL= extended-spectrum beta-lactamases.
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 preva- lence 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 bac- teria 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-gen- eration cephalosporins (> 50.0 %) and trimethoprim-sulfa- methoxazole (> 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 en- zymes 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. pneu- moniae 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 compro- mised 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 pa- tients 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. pneu- moniae) 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 serious- ness 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 infec- tions than younger patients. The literature has reported that older people may be more susceptible to different patholo- gies, due to natural physiological changes that may influence the immune system status (Sadighi Akha, 2018).
In this study, a trend of higher prevalence of antibiot- ic-resistant bacteria was observed with age, which may be an important criterion regarding the sensitivity of some antibi- otics. 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-pro- ducing 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 report- ed 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 bac- teria 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 inter- action 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 coun-
tries 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 stud- ies 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 con- text 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.
Updated information about the prevalence of bacterial species that cause infections in patients of different hospi- tal 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.
The authors thank the Hospital General del Estado of Hermo- sillo, the Universidad de Sonora, the Centro de Investigación en Alimentación y Desarrollo (CIAD, A.C.) and the CONSEJO NACIONAL DE HUMANIDADES, CIENCIA Y TECNOLOGÍA of
Mexico (CONAHCyT) for making this work possible.
The authors declare no conflict of interest.
Arias-Flores, R., Rosado-Quiab, U., Vargas-Valerio, A., and Grajales-Muñiz, C. 2016. Los microorganismos causantes de infecciones nosocomiales en el Instituto Mexicano del Seguro Social. Revista Médica del Instituto Mexicano del Seguro Social. 54: 20-4.
Banin, E., Hughes, D., and Kuipers, O.P., 2017. Editorial: Bacterial pathogens, antibiotics and antibiotic resistance. FEMS Microbiology Reviews. 41: 450-452.
Berhe, D.F., Beyene, G.T., Seyoum, B., Gebre, M., Haile, K., Tsegaye,
M., Boltena, M.T., Tesema, E., Kibret, T.C., Biru, M., Siraj, D.S., Shirley, D., Howe, R., and Abdissa, A. 2021. Prevalence of antimicrobial resistance and its clinical implications in Ethiopia: a systematic review. Antimicrobial Resistance & Infection Control. 10: 168-182.
Breijyeh, Z., Jubeh, B., and Karaman, R. 2020. Resistance of Gram-negative bacteria to current antibacterial agents and approaches to resolve it. Molecules. 25: 1340-1363.
Cocker, D., Chidziwisano, K., Mphasa, M., Mwapasa, T., Lewis, J.M., Rowlingson, B., Sammarro, M., Bakali, W., Salifu, C., Zuza, A., Charles, M., Mandula, T., Maiden, V., Amos, S., Jacob, S.T., Kajumbula, H., Mugisha, L., Musoke, D., Byrne, R., Edwards, T., Lester, R., Elviss, N., Roberts, A., Singer, A.C., Jewell, C., Morse, T., and Feasey, N.A. 2022. Investigating risks for human colonisation with extended spectrum beta-lactamase producing E. coli and K. pneumoniae in Malawian households: a one health longitudinal cohort study. medRxiv.
Garza-González, E., Morfín-Otero, R., Mendoza-Olazarán, S., Bocanegra-Ibarias, P., Flores-Treviño, S., Rodríguez-Noriega, E., Ponce-de-León, A., Sanchez-Francia, D., Franco-Cendejas, R., Arroyo-Escalante, S., Velázquez-Acosta, C., Rojas-Larios, F., Quintanilla, L.J., Maldonado-Anicacio, J.Y., Martínez-Miranda, R., Ostos-Cantú, H.L., Gomez-Choel, A., Jaime-Sanchez, J.L., Avilés-Benítez, L.K., Feliciano-Guzmán, J.M., Peña-López, C.D., Couoh-May, C.A., Molina-Jaimes, A., Vázquez -Narvaez, E.G., Rincón-Zuno, J., Rivera-Garay, R., Galindo-Espinoza, A., Martínez-Ramirez, A., Mora, J.P., Corte- Rojas, R.E., López- Ovilla, I., Monroy-Colin, V.A., Barajas-Magallón, J.M., Morales- De-la-Peña, C.T., Aguirre-Burciaga, E., Coronado-Ramírez, M., Rosales-García, A.A., Ayala-Tarín, M.-J., Sida-Rodríguez, S., Pérez-Vega, B.A., Navarro-Rodríguez, A., Juárez-Velázquez, G.E., Cetina-Umaña, C.M., Mena-Ramírez, J.P., Canizales- Oviedo, J., Moreno-Méndez, M.I., Romero-Romero, D., Arévalo-Mejía, A., Cobos-Canul, D.I., Aguilar-Orozco, G., Silva-Sánchez, J., and Camacho-Ortiz, A. 2019. A snapshot of antimicrobial resistance in Mexico. Results from 47 centers from 20 states during a six-month period. PLoS ONE. 14(3): e0209865.
Gupta, V., and Datta, P. 2019. Next-generation strategy for treating drug resistant bacteria: antibiotic hybrids. Indian Journal of Medical Research. 149(2): 97-106.
Hermann, J.C., Hensen, C., Ridder, L., Mulholland, A.J., and Höltje, H.-D. 2005. Mechanisms of antibiotic resistance: QM/MM modeling of the acylation reaction of a class a β-lactamase with benzylpenicillin. Journal of the American Chemical
Society. 127: 4454-4465.
Huang, H., Chen, B., Liu, G., Ran, J., Lian, X., Huang, X., Wang, N., and Huang, Z. 2018. A multi-center study on the risk factors of infection caused by multi-drug resistant Acinetobacter baumannii. BMC Infectious Diseases. 18(1): 11-17.
Humphries, D.L., Scott, M.E., and Vermund, S.H. (Eds.), 2021. Nutrition and infectious diseases: shifting the clinical paradigm. Springer International Publishing, Cham.
Jernigan, J.A., Hatfield, K.M., Wolford, H., Nelson, R.E., Olubajo, B., Reddy, S.C., McCarthy, N., Paul, P., McDonald, L.C., Kallen, A., Fiore, A., Craig, M., and Baggs, J. 2020. Multidrug-resistant bacterial infections in U.S. hospitalized patients, 2012–2017. The New England Journal of Medicine. 382(14): 1309-1319.
Kadel, S., and Kovats, S. 2018. Sex hormones regulate innate immune cells and promote sex differences in respiratory virus infection. Frontiers in Immunology. 9: 1653-1668.
Khouja, T., Mitsantisuk, K., Tadrous, M., and Suda, K.J., 2022. Global consumption of antimicrobials: im-pact of the WHO Global Action Plan on Antimicrobial Resistance and 2019 coronavirus pan-demic (COVID-19). Journal of Antimicrobial Chemotherapy 77, 1491-1499.
Klein, S.L., and Flanagan, K.L. 2016. Sex differences in immune responses. Nature Reviews Immunology. 16: 626-638.
López-Jácome, L.E., Fernández-Rodríguez, D., Franco-Cendejas, R., and Camacho-Ortiz, A., 2022. Increment antimicrobial resistance during the COVID-19 pandemic: Results from the Invifar Network. Antimicrobial Resistance. 28(3): 338-345.
López-Pueyo, M.J., Barcenilla-Gaite, F., Amaya-Villar, R., and Garnacho-Montero, J. 2011. Multirresistencia antibiótica en unidades de críticos. Medicina Intensiva. 35: 41-53.
Marín, M., and Gudiol, F. 2003. Antibióticos betalactámicos. Enfermedades Infecciosas y Microbiología Clínica. 27(2): 116-129.
Martin, D., Fougnot, S., Grobost, F., Thibaut-Jovelin, S., Ballereau, F., Gueudet, T., de Mouy, D., Robert, J., Alexandre, F., Andorin, P., Artur, F., Banctel, H., Bayette, J., Bonfils, F., Boraud, D., Camiade, S., Caillon, J., Capron, N., Chatelain, N., Coudé du Foresto, B., Cous, G., Desroys du Roure, V., Doermann, H.-P., Dubouix, A., Fougnot, S., Galinier, J.-L., Grandjean, G., Grisard, D., Grobost, F., Gueudet, T., Hance, P., Holstein, A., Jendrysik, M.-F., Jobert, E., Kamdem-Djoko, J.-R., Lair, D., Le
Bris, J.-M., Lecordier, N., Liébault, S., Lièvre, N., Nalpas, J.,
Payro, G., Poirey, B., Pradier, E., Prots, L., Rault, J.-P., Roche,
M.-L., Thierry, J., Valade, H., Versini, P., Vrain, A., and Weber,
P. 2016. Prevalence of extended-spectrum beta-lactamase producing Escherichia coli in community-onset urinary tract infections in France in 2013. Journal of Infection. 72(2): 201- 206.
More People Died of Antibiotic-Resistant “Superbugs” Than HIV/ AIDS In 2019; Sub-Saharan Africa Worst Affected - Health Policy Watch, 2022. URL https://healthpolicy-watch.news/ antimicrobial-resistance-to-bacterial-infections-killed- more-people-than-hiv-aids-in-2019-new-lancet-study- shows/ (accessed 2.23.23).
Murray, C.J., Ikuta, K.S., Sharara, F., Swetschinski, L., Robles Aguilar, G., Gray, A., Han, C., Bisignano, C., Rao, P., Wool, E.,
Johnson, S.C., Browne, A.J., Chipeta, M.G., Fell, F., Hackett, S., Haines-Woodhouse, G., Kashef Hamadani, B.H., Kumaran, E.A.P., McManigal, B., Agarwal, R., Akech, S., Albertson, S., Amuasi, J., Andrews, J., Aravkin, A., Ashley, E., Bailey, F., Baker, S., Basnyat, B., Bekker, A., Bender, R., Bethou, A., Bielicki, J., Boonkasidecha, S., Bukosia, J., Carvalheiro, C., Castañeda- Orjuela, C., Chansamouth, V., Chaurasia, S., Chiurchiù, S., Chowdhury, F., Cook, A.J., Cooper, B., Cressey, T.R., Criollo- Mora, E., Cunningham, M., Darboe, S., Day, N.P.J., De Luca,
M., Dokova, K., Dramowski, A., Dunachie, S.J., Eckmanns, T., Eibach, D., Emami, A., Feasey, N., Fisher-Pearson, N., Forrest, K., Garrett, D., Gastmeier, P., Giref, A.Z., Greer, R.C., Gupta, V., Haller, S., Haselbeck, A., Hay, S.I., Holm, M., Hopkins, S., Iregbu, K.C., Jacobs, J., Jarovsky, D., Javanmardi, F., Khorana, M., Kissoon, N., Kobeissi, E., Kostyanev, T., Krapp, F., Krumkamp, R., Kumar, A., Kyu, H.H., Lim, C., Limmathurotsakul, D., Loftus, M.J., Lunn, M., Ma, J., Mturi, N., Munera-Huertas, T., Musicha, P., Mussi-Pinhata, M.M., Nakamura, T., Nanavati, R., Nangia, S., Newton, P., Ngoun, C., Novotney, A., Nwakanma, D., Obiero, C.W., Olivas-Martinez, A., Olliaro, P., Ooko, E., Ortiz-Brizuela, E., Peleg, A.Y., Perrone, C., Plakkal, N., Ponce-de-Leon, A., Raad, M., Ramdin, T., Riddell, A., Roberts, T., Robotham, J.V., Roca, A., Rudd, K.E., Russell, N., Schnall, J., Scott, J.A.G., Shivamallappa, M., Sifuentes-Osornio, J., Steenkeste, N., Stewardson, A.J., Stoeva, T., Tasak, N., Thaiprakong, A., Thwaites, G., Turner, C., Turner, P., van Doorn, H.R., Velaphi, S., Vongpradith, A., Vu, H., Walsh, T., Waner, S., Wangrangsimakul, T., Wozniak, T., Zheng, P., Sartorius, B., Lopez, A.D., Stergachis, A., Moore, C., Dolecek, C., and Naghavi, M. 2022. Global burden of bacterial antimicrobial resistance in 2019: a systematic analysis. The Lancet. 399, 629-655.
Navarro-Navarro, M., Robles-Zepeda, R.E., Garibay-Escobar, A., and Ruiz-Bustos, E. 2011. Escherichia coli y Klebsiella pneumoniae comunitarias y hospitalarias productoras de β-lactamasas en hospitales de Hermosillo, Sonora. Salud Pública de México. 54(4): 341-344.
Patel, J., Harant, A., Fernandes, G., Mwamelo, A.J., Hein, W., Dekker, D., and Sridhar, D. 2023. Measuring the global response to antimicrobial resistance, 2020–21: a systematic governance analysis of 114 countries. The Lancet Infectious Diseases. S1473309922007964.
Rello, J., Kalwaje Eshwara, V., Lagunes, L., Alves, J., Wunderink, R.G., Conway-Morris, A., Rojas, J.N., Alp, E., and Zhang, Z. 2019. A global priority list of the TOp TEn resistant microorganisms (TOTEM) study at intensive care: a prioritization exercise based on multi-criteria decision analysis. European Journal of Clinical Microbiology & Infectious Diseases. 38(2): 319- 323.
Resistenciaantimicrobiana[WWWDocument], 2023. URLhttps:// www.insp.mx/lineas-de-investigacion/medicamentos-en- salud-publica/investigacion/resistencia-antimicrobiana. html (accessed 2.24.23).
Rolain, J.-M., Abat, C., Jimeno, M.-T., Fournier, P.-E., and Raoult,
D. 2016. Do we need new antibiotics? Clinical Microbiology and Infection. 22(5): 408-415.
Russ, D., Glaser, F., Shaer Tamar, E., Yelin, I., Baym, M., Kelsic, E.D., Zampaloni, C., Haldimann, A., and Kishony, R. 2020. Escape mutations circumvent a tradeoff between resistance to a beta-lactam and resistance to a beta-lactamase inhibitor. Nature Communications. 11(1): 2029-2038.
Sadighi Akha, A.A. 2018. Aging and the immune system: an overview. Journal of Immunological Methods. 463: 21-26.
Tejada Llacsa, P.J., Huarcaya, J.M., Melgarejo, G.C., Gonzales, L.F., Cahuana, J., Pari, R.M., Bohorquez, H.L., and Chacaltana,
J. 2015. Caracterización de infecciones por bacterias productoras de BLEE en un hospital de referencia nacional. Anales de la Facultad de Medicina. 76(2): 161-166.
Torres Soto, N.Y., López Franco, G., Torres Soto, N.A., Aray Roa, A., Monzalvo Curiel, A., Peña Torres, E.F., and Rojas Armadillo,
M.D.L., 2022. Risk perception about the covid-19 pandemic and its effect on self-medication practices in population of northwestern Mexico. Acta Universitaria 32, 1-14.
vom Steeg, L.G., and Klein, S.L. 2016. SeXX matters in infectious disease pathogenesis. PLoS Pathogens. 12(2): e1005374.
Zúniga-Moya, J.C., Bejarano-Cáceres, S., Valenzuela-Cervantes, H., Gough-Coto, S., Castro-Mejía, A., Chinchilla-López, C., Díaz-Mendoza, T., Hernández-Rivera, S., and Martínez-López,
J. 2016. Antibiotic sensitivity profile of bacteria in urinary tract infections. Acta Médica Costarricense. 58(4): 146-153.