Next Article in Journal
Antibacterial and Anti-Biofilm Activity of Pyrones from a Pseudomonas mosselii Strain
Next Article in Special Issue
Functional Characterization, Mechanism, and Mode of Action of Putative Streptomycin Adenylyltransferase from Serratia marcescens
Previous Article in Journal
Experimental and In Silico Evaluation of New Heteroaryl Benzothiazole Derivatives as Antimicrobial Agents
Previous Article in Special Issue
Anti-Restriction Gene Homologs Are Highly Represented in Methicillin-Resistant and Multidrug-Resistant Staphylococcus aureus ST239 and ST398: Implications for Resistance Gene Acquisitions
 
 
Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
Journals
Antibiotics
Volume 11
Issue 11
10.3390/antibiotics11111656
antibiotics-logo
Submit to this Journal Review for this Journal Propose a Special Issue
► Article Menu

Article Menu

share Share announcement Help format_quote Cite question_answer Discuss in SciProfiles thumb_up
...
Endorse textsms
...
Comment
first_page
settings
Order Article Reprints
Font Type:
Arial Georgia Verdana
Font Size:
Aa Aa Aa
Line Spacing:
Column Width:
Background:
Article

Limited Therapeutic Options in Mexico for the Treatment of Urinary Tract Infections

by
Guadalupe Miranda-Novales
1,2,*,
Karen Flores-Moreno
2,
Yolanda López-Vidal
3,
Samuel Ponce de León-Rosales
4 and
PUCRA Network Members
†
1
Analysis and Synthesis of Evidence Research Unit, Mexican Institute of Social Security, Mexico City 06720, Mexico
2
Microbiome Laboratory, Faculty of Medicine, National Autonomous University of Mexico, Mexico City 04360, Mexico
3
Microbiology and Parasitology Department, Faculty of Medicine, National Autonomous University of Mexico, Mexico City 04360, Mexico
4
University Program for Health Research, National Autonomous University of Mexico, Mexico City 04510, Mexico
*
Author to whom correspondence should be addressed.
†
PUCRA Network Members: Listed in Acknowledgments.
Antibiotics 2022, 11(11), 1656; https://doi.org/10.3390/antibiotics11111656
Submission received: 27 September 2022 / Revised: 25 October 2022 / Accepted: 27 October 2022 / Published: 18 November 2022
(This article belongs to the Special Issue Resistant Bacteria: Molecular Studies and Antimicrobial Resistance)
Browse Figure
Review Reports Versions Notes

Abstract

:
The rise in antimicrobial resistance (AMR) has complicated the management of urinary tract infections (UTIs). The objective of this study was to evaluate the antimicrobial susceptibility patterns of Escherichia coli and Klebsiella pneumoniae. Design: prospective observational study. Bacteria were classified as susceptible or resistant to ampicillin-sulbactam, amikacin, gentamicin, ciprofloxacin, norfloxacin, nitrofurantoin, trimethoprim-sulfamethoxazole (TMP/SMZ), ertapenem, meropenem, and fosfomycin. The sensitivity to fosfomycin and chloramphenicol was evaluated by the disk diffusion method. Statistical analysis: the chi-square test and Fisher’s exact test were used to compare differences between categories. A p value < 0.05 was considered statistically significant. Isolates were collected from January 2019 to November 2020 from 21 hospitals and laboratories. A total of 238 isolates were received: a total of 156 E. coli isolates and 82 K. pneumoniae isolates. The majority were community-acquired infections (64.1%). Resistance was >20% for beta-lactams, aminoglycosides, fluoroquinolones, and TMP/SMZ. For E. coli isolates, resistance was <20% for amikacin, fosfomycin, and nitrofurantoin; for K. pneumoniae, amikacin, fosfomycin, chloramphenicol, and norfloxacin. All were susceptible to carbapenems. K. pneumoniae isolates registered a higher proportion of extensively drug-resistant bacteria in comparison with E. coli (p = 0.0004). In total, multidrug-resistant bacteria represented 61% of all isolates. Isolates demonstrated high resistance to beta-lactams, fluoro-quinolones, and TMP/SMZ.

1. Introduction

Urinary tract infections (UTIs) are one of the most common reasons for consultation that involves the prescription of an antibiotic. Several guidelines allow the use of empirical antibiotics without the need for a urine culture and a susceptibility report on the causal agent. For many years, this was a common and accepted practice at the first level of care, mostly in cases of acute uncomplicated cystitis. The notable rise in antimicrobial resistance (AMR) has complicated the management and efficacy of empirical antibiotics and constitutes a real challenge [1]. It is believed that UTIs represent a multi-positional problem, as they result in a decrease in quality of life (QoL), especially in cases of recurrence, complications, and sequelae; they also consume a large amount of economic and human resources [2].
AMR resistance changes markedly in different geographical areas, and unfortunately, there are no periodic reports from all countries. A systematic review of AMR in uropathogens from the Asia-Pacific region found a prevalence of resistance against trimethoprim/sulfamethoxazole (TMP/SMZ), ciprofloxacin, and ceftriaxone from 33 to 90%, against nitrofurantoin from 2.7 to 31.4%, and against fosfomycin at 1.8% [3]. In contrast, a review from Iran showed that one of the most effective antibiotics for Escherichia coli was ciprofloxacin, along with nitrofurantoin, imipenem, and chloramphenicol [4]. One factor to consider in selecting an empirical antibiotic is the regional prevalence of antimicrobial multidrug-resistant (MDR) bacteria. Some reports have found this characteristic with a higher frequency in K. pneumoniae isolates (40.4%) in comparison with E. coli (23.3%) [5].
In 2017, the Universidad Nacional Autónoma de México (UNAM) proposed an action plan to control antimicrobial resistance in Mexico through the University Program for Health Research (Programa Universitario de Investigación en Salud, PUIS). One of the first tasks of this plan was to invite health personnel from institutions and laboratories to send information, thus establishing the status of antimicrobial resistance in Mexico (the PUCRA network is named after its acronym in Spanish: Plan Universitario de Control de la Resistencia Antimicrobiana). In the first report, information from 12,151 isolates from urine cultures collected during 2016 and 2017 (90% corresponded to Escherichia coli and 10% to Klebsiella pneumoniae) found that in E. coli, median resistance to amikacin, imipenem, meropenem, and nitrofurantoin was <10%; K. pneumoniae isolates also showed low resistance to amikacin and carbapenems, but median resistance to nitrofurantoin was 52%. For both enteric bacteria, median resistance to cephalosporins, ciprofloxacin, and TMP/SMZ was >40% [6]. Fosfomycin and chloramphenicol susceptibilities were not available. Another network in Mexico (Network for Research and Surveillance of Drug Resistance [Red Temática de Investigación y Vigilancia de la Farmacorresistencia (INVIFAR)]) reported high resistance (>40%) in E. coli since 2009 [7].
AMR resistance in uropathogens is recognized as a serious problem in Latin American countries. In an analysis of data obtained from the Global Burden of Diseases, Injuries, and Risk Factors Study, Escherichia coli and Klebsiella pneumoniae accounted for over 50% of the deaths attributable to and associated with AMR [8].
Before 2010, in Mexico, antibiotics were sold over the counter and AMR in common pathogens was in the top places in comparison with other Latin American countries. Some regulatory changes have been introduced. Today, a doctor’s prescription is needed to purchase an antibiotic at a drug store. There is no proper evaluation of the impact of the regulatory measure, but most of the local published information is consistent with an increase in AMR [9,10,11,12,13].
Fosfomycin is an old drug but an interesting candidate for the treatment of infections due to MDR bacteria [14,15]. Chloramphenicol, an old broad-spectrum antibiotic, has been included to understand the genomic diversity and genotypic presence of antimicrobial resistance in MDR E. coli and K. pneumoniae isolates by whole genome sequencing (WGS) [16].
The objective of this study was to evaluate the antimicrobial susceptibility patterns of Escherichia coli and Klebsiella pneumoniae isolates causing UTIs and to test in vitro antimicrobial susceptibility to fosfomycin and chloramphenicol.

2. Results

2.1. Origin of Isolates

Isolates Were Collected from January 2019 to November 2020

Twenty-one hospitals and laboratories from eight states of the Mexican Republic (12 located in Mexico City, two in Guanajuato, two in Puebla, and one each in Mexico State, Durango, Jalisco, Nuevo León, and Morelos) sent a minimum of ten urine culture isolates. Characteristics of hospitals/institutions: seven specialty hospitals, five general hospitals, three pediatric hospitals, three private reference laboratories, two tertiary-care centers, and one private hospital (Table 1).
In total, 238 isolates were received: 156 Escherichia coli isolates and 82 Klebsiella pneumoniae isolates. Most of the isolates corresponded to community-acquired infections (64.1%) from non-hospitalized (57.2%) and adult patients (>18 years, 87%). Escherichia coli isolates were more common in females (72%), with a similar sex distribution for Klebsiella pneumoniae isolates (52% in females and 48% in males).

2.2. Antimicrobial Susceptibility Patterns

Resistance was high for most of the tested antibiotics, including beta-lactams, aminoglycosides, fluoroquinolones, and TMP/SMZ. For E. coli isolates, resistance was less than 20% only for amikacin (0.6%), fosfomycin (9.5%), and nitrofurantoin (8%). For K. pneumoniae isolates, the antibiotics with the lowest resistance were amikacin (1%), fosfomycin (10%), chloramphenicol (16%), and norfloxacin (19%) (Figure 1). All isolates were susceptible to ertapenem and meropenem.

Extended Spectrum Beta-Lactamase Producers and MDR Bacteria

There was no difference in the frequency of ESBL producers between E. coli and K. pneumoniae isolates (56% vs. 52%, respectively, p = 0.62). E. coli ESBL-producers were more resistant than ESBL-negative isolates with a significant statistical difference (p < 0.01) for the following antibiotics: ampicillin/sulbactam, gentamicin, ciprofloxacin, and norfloxacin. For K. pneumoniae isolates, differences were greater for ampicillin/sulbactam, gentamicin, ciprofloxacin, nitrofurantoin, and TMP/SMZ. For two of them (gentamicin and TMP/SMZ), resistance dropped to < 20% (Table 2).
In agreement with these results, Klebsiella pneumoniae isolates registered a higher proportion of XDR bacteria compared to E. coli (p = 0.0004), although the number of isolates was low. However, for the E. coli isolates, the proportion of MDR bacteria showed a statistically significant difference in comparison with K. pneumoniae (68% vs. 48%). Overall, MDR bacteria represented the most frequent characteristic of all isolates (61%). There was no difference for isolates resistance to at least one antibiotic in two antimicrobial categories (p = 0.22) (Table 3).
A small number of isolates (n = 31) corresponded to pediatric patients. Seventy-four percent of them were E. coli. In comparison with isolates from adult patients, susceptibility patterns were similar (Table 4). A major problem was observed in K. pneumoniae, 7/8 isolates were ESBL producers and showed high resistance rates. Fosfomycin was the only active oral agent.

3. Discussion

To treat UTIs effectively, the correct antibiotic should be used at the correct dose for the shortest effective duration of therapy possible [17,18]. Regrettably, in some countries such as Mexico, clinical practice guidelines are not updated [19,20] and first-line empirical treatments still include TMP/SMZ, cephalexin, and amoxicillin, despite the availability of local information in several publications [6,7,10,11,12,13,21].
One of the consequences of the lack of adequate and prompt treatment is the progression of infection, leading to the development of a potentially fatal systemic infection, especially in high-risk patients. In the Global Prevalence of Infections in Urology (GPIU) study, the antibiotics most prescribed were fluoroquinolones (35%), cephalosporins (27%), and penicillin (16%). The resistance rates of all antibiotics tested against the isolates other than carbapenems were higher than 10% [22].
The results of this study validate the existence of the AMR problem in uropathogens. Most of the published information on ESBL-positive Enterobacteriaceae is from bloodstream and intraabdominal infections. In general, these isolates are also resistant to several antibiotics, such as fluoroquinolones and TMP/SMZ, which are no longer suitable for the empiric treatment of UTI [23]. In this study, which included isolates from outpatients, inpatients, and reference laboratories, demonstrated that more than half of the isolates were ESBL producers, both in community and healthcare-associated infections. Thus, oral options for the treatment of uncomplicated UTIs in Mexico are limited to nitrofurantoin and fosfomycin for E. coli, and only fosfomycin for K. pneumoniae isolates. Almost 70% of E.coli isolates were MDR, leaving amikacin and carbapenems as the only options for acute pyelonephritis and complicated cases.
Even in this reduced sample of pediatric patients, high resistance rates and MDR were the common features in most of the isolates, in contrast with other reports, with resistance rates to first line treatments between 10–40% [24]. We need to consider the referral bias in our population, as all pediatric patients are seen at a tertiary-care level hospital. Well-known risk factors such as pre-existing conditions, previous antibiotic treatments, and hospitalization contribute to the selection of resistant strains [25]. As shown in one study, discordant empirical UTI treatment in hospitalized children can be effective in 50% of the cases, but patients with risk factors need a different approach [26]. Half of the patients with a therapeutic failure to an empirical treatment is not acceptable. Before the antibiotic is prescribed, underlying conditions, drug interactions, recurrence of events, and renal function need to be evaluated in each case.
The crisis regarding available options will be worse for institutions with limited drugs (e.g., fosfomycin is not available in the Mexican Institute of Social Security). Over 50% of the isolates are MDR, so in some cases, the only alternative will be carbapenems. The increased use of this group of antibiotics is responsible for the collateral damage and the emergence of the carbapenem-resistant pathogens (enteric bacteria, Acinetobacter baumannii, and Pseudomonas sp.) Although chloramphenicol showed good in vitro activity, most of a chloramphenicol dose is metabolized by the liver into inactive products, and only 5–15% of chloramphenicol is excreted unchanged in the urine. Therefore, it is not a useful alternative for UTIs.
This study has several limitations: the clinical information is minimal, risk factors, characteristics of infection, pre-existing conditions, recent hospitalization, previous use of antibiotics, response to treatment, and outcome are not available. However, our results are consistent with several reports in the country and worldwide. There is an urgent need to implement antimicrobial stewardship programs targeting UTIs. Although most studies focus on adult patients, the principles are the same for all age groups. The five-D model includes correct diagnosis, the right drug, dose, and duration, and finally de-escalation (narrow spectrum antibiotics, or stopping antibiotics based on culture results) [27]. Anti- microbial stewardship programs have proven their effectiveness in urgent care [28] as well as in hospitalized patients with potentially fatal outcomes [29].
Since new effective antibiotics are not on the horizon, different alternatives to antibiotics are being evaluated: vaccines, small compounds targeting adhesion, urease, bacterial capsules, nutraceuticals, bacteriophages, and probiotics. Nevertheless, further research is needed before definitive recommendations can be issued [30,31].

4. Materials and Methods

Design: prospective observational. Institutions and laboratories in the PUCRA network were asked to send non-duplicate Escherichia coli and Klebsiella pneumoniae isolates. Inclusion criteria: patients of all ages and both sexes, diagnosed with a symptomatic UTI, regardless of acquisition (community or healthcare-associated infection), history of urologic procedures, previous infections, or prior antibiotic use. Only one non-duplicate isolate per patient was included. Exclusion criteria: asymptomatic bacteriuria.
Bacterial identification and determination of the antimicrobial susceptibility of each isolate were performed with standard microbiological techniques. Microbial identification was done with the GN ID card and testing of susceptibility to antimicrobial drugs was performed using the microdilution method (VITEK 2 XL® BioMérieux) with AST-271 and AST-272 cards. Bacteria were classified as producers of extended spectrum beta-lactamases (ESBL) and susceptible or resistant to ampicillin-sulbactam, amikacin, gentamicin, ciprofloxacin, norfloxacin, nitrofurantoin, TMP/SMZ, ertapenem, meropenem, and fosfomycin, according to the CLSI (Clinical and Laboratory Standards Institute) guidelines [32].
Sensitivity to fosfomycin and chloramphenicol was evaluated by the disk diffusion method, with fosfomycin 200 µg/50 µg of glucose 6-phosphate and chloramphenicol 30 µg disks (Oxoid TM). The Mueller–Hinton agar plates (BD TM) were incubated for 24 h at 35 °C and the susceptibility results for fosfomycin were interpreted according to the CLSI M100 [32] breakpoints (zone diameter, mm) for E. coli extrapolated to enteric bacteria (≥16 susceptible, 13–15 intermediate, and ≤12 resistant). Breakpoints for chloramphenicol are ≥18 susceptible, 13–17 intermediate, and ≤12 resistant. Escherichia coli ATCC® 25,922 was used as a quality control strain.
Definitions: MDR was defined as acquired non-susceptibility to at least one agent in three or more antimicrobial categories; XDR (extensively drug-resistant) was defined as non-susceptibility to at least one agent in all but two or fewer antimicrobial categories (i.e., bacterial isolates remain susceptible to only one or two categories); and PDR (pandrug-resistant) was defined as non-susceptibility to all agents in all antimicrobial categories [33].
Statistical analysis: Categorical data are presented as frequencies and percentages. The chi-square test and Fisher’s exact test were used to compare differences between categories. A p value < 0.05 was considered as statistically significant.
The study was conducted in accordance with the Declaration of Helsinki and approved by the Ethics and Research Commissions of the Faculty of Medicine and registered with the number: No. FM-DI/060/2019 on 5 January 2019. Patient consent was deemed unnecessary by the ethics and research commissions due to the design of the study and because data on isolates were not linked to an identifiable person.

5. Conclusions

Escherichia coli isolates demonstrated high resistance to beta-lactams, fluoroquinolones, and TMP/SMZ. For oral treatment in Mexico, only nitrofurantoin and fosfomycin remain as effective alternatives. For Klebsiella pneumoniae, the only active oral antibiotic is fosfomycin. Amikacin and carbapenems are the drugs of choice for complicated infections. MDR bacteria were the most frequent characteristic of all isolates (61%).

Author Contributions

Conceptualization, G.M.-N., K.F.-M. and S.P.d.L.-R.; methodology, K.F.-M., Y.L.-V., G.M.-N. and S.P.d.L.-R.; validation, Y.L.-V. and S.P.d.L.-R.; formal analysis, G.M.-N., K.F.-M., S.P.d.L.-R. and Y.L.-V.; writing—original draft preparation, G.M.-N. and K.F.-M.; writing—review and editing, Y.L.-V., S.P.d.L.-R. and G.M.-N.; funding acquisition, Y.L.-V. and K.F.-M. Network members: validation, review and editing. All authors have read and agreed to the published version of the manuscript.

Funding

This research was funded by Programa de Apoyo a Proyectos de Investigación e Innovación Tecnológica (PAPIIT) project number IN218220 and Donación GlaxoSmithKline México, S.A. de C.V. para la Red de Vigilancia de la Resistencia Antimicrobiana.

Institutional Review Board Statement

The study was conducted in accordance with the Declaration of Helsinki and approved by the Ethics and Research Commissions of the Faculty of Medicine and registered with the number No. FM-DI/060/2019 on 5 January 2019.

Informed Consent Statement

Patient consent was deemed unnecessary by the ethics and research commissions due to the design of the study and because data on isolates were not linked to an identifiable person.

Data Availability Statement

Databases supporting the results can be provided upon request.

Acknowledgments

We are grateful for the support of the Coordinación de la Investigación Científica, National Autonomous University of Mexico. List of PUCRA Network Members: Soto-Hernández JL; Ángeles-Morales V (Instituto Nacional de Neurología y Neurocirugía “Manuel Velasco Suárez”); Vilar-Compte D; Volkow-Fernández P; Velázquez-Acosta C (Instituto Nacional de Cancerología); Soto-Nieto GI, Vázquez-Larios MR (Instituto Nacional de Cardiología “Ignacio Chávez”); Arroyo-Escalante S; Ramírez-Hinojosa JP; Rodríguez-Zuleta P (Hospital General “Manuel Gea González”); Cruz-García E; Meza-Chávez A; Ramos-Hernández JM (UMAE Hospital de Cardiología “Luis Méndez”; CMN Siglo XXI); Morfín-Otero MR; Rodríguez-Noriega E; Pérez-Gómez HR; Esparza-Ahumada S (Hospital Civil de Guadalajara “Fray Antonio Alcalde”); Basurto-Chipolini DA; Reyes-Aguayo M (Hospital General Regional No. 200 Tecámac); Hernández-Medel ML; Morales-Gil MA (Hospital General de México “Eduardo Liceaga”); Tinoco-Favila JC; Salcido-Gutiérrez L (Hospital General de Durango); Molina-Gamboa JD; García-Torres RI (UMAE 34 Hospital de Cardiología Monterrey); Castellanos-Martínez JM; Gil-Veloz M; Rivera-Garay LR (Hospital Regional de Alta Especialidad del Bajío); Domínguez-Sosa F; Flores-Romero MP (Hospital Central Sur de Alta Especialidad de Petróleos Mexicanos); Ruiz-Argüelles A; Acosta-Sandria L; Velásquez-Ramírez DG (Laboratorios Ruiz Puebla); Franco-Cendejas R; López-Jácome LE (Instituto Nacional de Rehabilitación “Luis Guillermo Ibarra Ibarra”); Vázquez-Rosales JG; Labra-Zamora G (UMAE Hospital de Pediatría CMN Siglo XXI); Ruiz-Jiménez M (Asesores Especializados en Laboratorios, Puebla); Macías-Hernández A, González-Aguilar EE (Hospital Aranda de la Parra); Rodríguez-Martínez SE; Jiménez-Ramírez AK; Gallegos-Rodríguez D (CARPERMOR Laboratorio de Referencia Internacional); Arias-de la Garza E; Sánchez-Francia D (Hospital del Niño Morelense); Martínez-Orozco JA; Becerril-Vargas E; Mireles-Dávalos CD (Instituto Nacional de Enfermedades Respiratorias “ Ismael Cosío Villegas”); Álvarez-Hernández L and; Rodríguez-Silva S (Hospital Pediátrico de la Villa).

Conflicts of Interest

The authors declare no conflict of interest.

References

  1. Paul, R. State of the Globe: Rising Antimicrobial Resistance of Pathogens in Urinary Tract Infection. J. Glob. Infect. Dis. 2018, 10, 117–118. [Google Scholar] [CrossRef] [PubMed]
  2. Behzadi, P.; Urbán, E.; Matuz, M.; Benkő, R.; Gajdács, M. The role of Gram-negative bacteria in urinary tract infections: Current concepts and therapeutic options. Adv. Exp. Med. Biol. 2021, 1323, 35–69. [Google Scholar] [CrossRef] [PubMed]
  3. Sugianli, A.K.; Ginting, F.; Parwati, I.; de Jong, M.D.; van Leth, F.; Schultsz, C. Antimicrobial resistance among uropathogens in the Asia-Pacific region: A systematic review. JAC Antimicrob. Resist. 2021, 3, dlab003. [Google Scholar] [CrossRef] [PubMed]
  4. Mortazavi-Tabatabaei, S.A.R.; Ghaderkhani, J.; Nazari, A.; Sayehmiri, K.; Sayehmiri, F.; Pakzad, I. Pattern of antibacterial resistance in urinary tract infections: A systematic review and meta-analysis. Int. J. Prev. Med. 2019, 10, 169. [Google Scholar] [CrossRef] [PubMed]
  5. Silva, A.; Costa, E.; Freitas, A.; Almeida, A. Revisiting the frequency and antimicrobial resistance patterns of bacteria implicated in community urinary tract infections. Antibiotics 2022, 11, 768. [Google Scholar] [CrossRef]
  6. Miranda-Novales, M.G.; Flores-Moreno, K.; López-Vidal, Y.; Rodríguez-Álvarez, M.; Solórzano-Santos, F.; Soto-Hernández, J.L.; Ponce de León-Rosales, S. UNCAR Network*. Antimicrobial resistance and antibiotic consumption in Mexican hospitals. Salud. Publica. Mex. 2020, 62, 42–49. [Google Scholar] [CrossRef]
  7. Garza-González, E.; Franco-Cendejas, R.; Morfín-Otero, R.; Echaniz-Aviles, G.; Rojas-Larios, F.; Bocanegra-Ibarias, P.; Flores-Treviño, S.; Ponce-De-León, A.; Rodríguez-Noriega, E.; Alavez-Ramírez, N.; et al. The Evolution of Antimicrobial Resistance in Mexico During the Last Decade: Results from the INVIFAR Group. Microb. Drug Resist. 2020, 26, 1372–1382. [Google Scholar] [CrossRef]
  8. Li, X.; Fan, H.; Zi, H.; Hu, H.; Li, B.; Huang, J.; Luo, P.; Zeng, X. Global and regional burden of bacterial antimicrobial resistance in urinary tract infections in 2019. J. Clin. Med. 2022, 11, 2817. [Google Scholar] [CrossRef]
  9. Amabile-Cuevas, C.F. Antibiotic usage and resistance in Mexico: An update after a decade of change. J. Infect. Dev. Ctries. 2021, 15, 442–449. [Google Scholar] [CrossRef]
  10. Zavala-Cerna, M.G.; Segura-Cobos, M.; Gonzalez, R.; Zavala-Trujillo, I.G.; Navarro-Perez, S.F.; Rueda-Cruz, J.A.; Santoscoy-Tovar, F.A. The clinical significance of high antimicrobial resistance in community-acquired urinary tract infections. Can J. Infect. Dis. Med. Microbiol. 2020, 2020, 2967260. [Google Scholar] [CrossRef]
  11. Paniagua-Contreras, G.L.; Monroy-Pérez, E.; Bautista, A.; Reyes, R.; Vicente, A.; Vaca-Paniagua, F.; Díaz, C.E.; Martínez, S.; Domínguez, P.; García, L.R.; et al. Multiple antibiotic resistances and virulence markers of uropathogenic Escherichia coli from Mexico. Pathog. Glob. Health 2018, 112, 415–420. [Google Scholar] [CrossRef] [PubMed]
  12. Ramírez-Castillo, F.Y.; Moreno-Flores, A.C.; Avelar-González, F.J.; Márquez-Díaz, F.; Harel, J.; Guerrero-Barrera, A.L. An evaluation of multidrug-resistant Escherichia coli isolates in urinary tract infections from Aguascalientes, Mexico: Cross-sectional study. Ann. Clin. Microbiol. Antimicrob. 2018, 17, 34. [Google Scholar] [CrossRef] [PubMed]
  13. Lagunas-Rangel, F.A. Antimicrobial susceptibility profiles of bacteria causing urinary tract infections in Mexico: Single-centre experience with 10 years of results. J. Glob. Antimicrob. Resist. 2018, 14, 90–94. [Google Scholar] [CrossRef] [PubMed]
  14. Patwardhan, V.; Singh, S. Fosfomycin for the treatment of drug-resistant urinary tract infections: Potential of an old drug not explored fully. Int. Urol. Nephrol. 2017, 49, 1637–1643. [Google Scholar] [CrossRef]
  15. Albán, M.V.; Mariño-Brito, E.; Villavicencio, F.; Satán, C.; Villacís, J.E.; Gestal, M.C. Fosfomycin, applying known methods and remedies to a new era. Diseases 2020, 8, 31. [Google Scholar] [CrossRef]
  16. Moghnia, O.H.; Al-Sweih, N.A. Whole genome sequence analysis of multidrug resistant Escherichia coli and Klebsiella pneumoniae strains in Kuwait. Microorganisms 2022, 10, 507. [Google Scholar] [CrossRef]
  17. Abbott, I.J.; Peel, T.N.; Cairns, K.A.; Stewardson, A.J. Antibiotic management of UTI in the post-antibiotic era: A narrative review highlighting diagnostic and antimicrobial stewardship. Clin. Microbiol. Infect. 2022, S1198-743X(22)00272-5. [Google Scholar] [CrossRef]
  18. Kulchavenya, E. The best rules for antimicrobial stewardship in urogenital tract infections. Curr. Opin. Urol. 2020, 30, 838–844. [Google Scholar] [CrossRef]
  19. Diagnóstico y tratamiento de la infección de vías urinarias no complicada en menores de 18 años en el primer y segundo niveles de atención. In Guía de Práctica Clínica: Evidencias y Recomendaciones; CENETEC: Mexico City, Mexico, 2021. Available online: http://www.cenetec-difusion.com/CMGPC/GPC-SS027-21/ER.pdf (accessed on 8 August 2022).
  20. Diagnóstico y Tratamiento de la Infección Aguda, no Complicada del Tracto Urinario de la Mujer México: Instituto Mexicano del Seguro Social 2009. Available online: https://www.imss.gob.mx/sites/all/statics/guiasclinicas/077GER.pdf (accessed on 8 August 2022).
  21. Ballesteros-Monrreal, M.G.; Arenas-Hernández, M.M.; Enciso-Martínez, Y.; Martínez-de la Peña, C.F.; Rocha-Gracia, R.D.C.; Lozano-Zaraín, P.; Navarro-Ocaña, A.; Martínez-Laguna, Y.; de la Rosa-López, R. Virulence and resistance determinants of uropathogenic Escherichia coli strains isolated from pregnant and non-pregnant women from two states in Mexico. Infect. Drug Resist. 2020, 13, 295–310. [Google Scholar] [CrossRef] [Green Version]
  22. Wagenlehner, F.; Tandogdu, Z.; Bartoletti, R.; Cai, T.; Cek, M.; Kulchavenya, E.; Köves, B.; Naber, K.; Perepanova, T.; Tenke, P.; et al. The Global prevalence of infections in urology study: A long-term, worldwide surveillance study on urological infections. Pathogens 2016, 5, 10. [Google Scholar] [CrossRef]
  23. Mazzariol, A.; Bazaj, A.; Cornaglia, G. Multi-drug-resistant Gram-negative bacteria causing urinary tract infections: A review. J. Chemother. 2017, 29, 2–9. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  24. Pierantoni, L.; Andreozzi, L.; Ambretti, S.; Dondi, A.; Biagi, C.; Baccelli, F.; Lanari, M. Three-Year Trend in Escherichia coli Antimicrobial Resistance among Children’s Urine Cultures in an Italian Metropolitan Area. Children 2021, 8, 597. [Google Scholar] [CrossRef] [PubMed]
  25. Fan, N.C.; Chen, H.H.; Chen, C.L.; Ou, L.S.; Lin, T.Y.; Tsai, M.H.; Chiu, C.H. Rise of community-onset urinary tract infection caused by extended-spectrum β-lactamase-producing Escherichia coli in children. J. Microbiol. Immunol. Infect. 2014, 47, 399–405. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  26. Autore, G.; Neglia, C.; Di Costanzo, M.; Ceccoli, M.; Vergine, G.; La Scola, C.; Malaventura, C.; Falcioni, A.; UTI-Ped-ER Study Group. Clinical Outcome of Discordant Empirical Therapy and Risk Factors Associated to Treatment Failure in Children Hospitalized for Urinary Tract Infections. Children 2022, 9, 128. [Google Scholar] [CrossRef] [PubMed]
  27. Goebel, M.C.; Trautner, B.W.; Grigoryan, L. The Five Ds of Outpatient Antibiotic Stewardship for Urinary Tract Infections. Clin. Microbiol. Rev. 2021, 34, e0000320. [Google Scholar] [CrossRef]
  28. Nedved, A.; Lee, B.R.; Hamner, M.; Wirtz, A.; Burns, A.; El Feghaly, R.E. Impact of an antibiotic stewardship program on antibiotic choice, dosing, and duration in pediatric urgent cares. Am. J. Infect. Control. 2022, S0196-655300597-1. [Google Scholar] [CrossRef]
  29. Muratore, E.; Baccelli, F.; Leardini, D.; Campoli, C.; Belotti, T.; Viale, P.; Prete, A.; Pession, A.; Masetti, R.; Zama, D. Antimicrobial Stewardship Interventions in Pediatric Oncology: A Systematic Review. J. Clin. Med. 2022, 11, 4545. [Google Scholar] [CrossRef]
  30. Loubet, P.; Ranfaing, J.; Dinh, A.; Dunyach-Remy, C.; Bernard, L.; Bruyère, F.; Lavigne, J.P.; Sotto, A. Alternative therapeutic options to antibiotics for the treatment of urinary tract infections. Front. Microbiol. 2020, 11, 1509. [Google Scholar] [CrossRef]
  31. De Nunzio, C.; Bartoletti, R.; Tubaro, A.; Simonato, A.; Ficarra, V. Role of D-Mannose in the Prevention of Recurrent Uncomplicated Cystitis: State of the Art and Future Perspectives. Antibiotics 2021, 10, 373. [Google Scholar] [CrossRef]
  32. Clinical and Laboratory Standards Institute (CLSI) M100—Performance Standards for Antimicrobial Susceptibility Testing, 31st ed.; Clinical and Laboratory Standards Institute: Wayne, PA, USA, 20 September 2021; Available online: https://clsi.org/media/3481/m100ed30_sample.pdf (accessed on 20 September 2022).
  33. Magiorakos, A.P.; Srinivasan, A.; Carey, R.B.; Carmeli, Y.; Falagas, M.E.; Giske, C.G.; Harbarth, S.; Hindler, J.F.; Kahlmeter, G.; Olsson-Liljequist, B.; et al. Multidrug-resistant, extensively drug-resistant and pandrug-resistant bacteria: An international expert proposal for interim standard definitions for acquired resistance. Clin. Microbiol. Infect. 2012, 18, 268–281. [Google Scholar] [CrossRef]
Antibiotics 11 01656 g001 550
Figure 1. Antibiotic resistance percentages in Escherichia coli (n = 156) and Klebsiella pneumoniae (n = 82) isolates from urine cultures.
Figure 1. Antibiotic resistance percentages in Escherichia coli (n = 156) and Klebsiella pneumoniae (n = 82) isolates from urine cultures.
Antibiotics 11 01656 g001
Table
Table 1. Characteristics of hospitals/institutions participating in the study.
Table 1. Characteristics of hospitals/institutions participating in the study.
Name of Hospital or Institution (Location)Type of HospitalNumber of Beds
1. Instituto Nacional de Neurología y Neurocirugía “Dr. Manuel Velasco Suárez” (Mexico City)Specialty (neurology and neurosurgery)126
2. Instituto Nacional de Cancerología (Mexico City)Specialty (oncology)188
3. Instituto Nacional de Cardiología “Dr. Ignacio Chávez” (Mexico City)Specialty (cardiology)213
4. Hospital General “Dr. Manuel Gea González” (Mexico City)General107
5. UMAE Hospital de Cardiología “Dr. Luis Méndez”, Centro Médico Nacional Siglo XXI, IMSS (Mexico City)Specialty (cardiology)170
6. Hospital Civil de Guadalajara “Fray Antonio Alcalde” (Jalisco)General843
7. Hospital General Regional Nº 200 Tecámac, IMSS (State of Mexico)General (regional)249
8. Hospital General de México “Dr. Eduardo Liceaga” (Mexico City)General842
9. Hospital General de Durango (Durango)General126
10. UMAE 34 Hospital de Cardiología Monterrey, IMSS (Nuevo León)Specialty (cardiology)200
11. Hospital Regional de Alta Especialidad del Bajío (Guanajuato)Tertiary-care (regional)184
12. Hospital Central Sur de Alta Especialidad de Petróleos Mexicanos (Mexico City)Tertiary-care140
13. Laboratorios Ruiz (Puebla)Private laboratoryNot applicable
14. Instituto Nacional de Rehabilitación “Luis Guillermo Ibarra Ibarra” (Mexico City)Specialty 228
15. UMAE de Pediatría, Centro Médico Nacional Siglo XXI, IMSS (Mexico City) Specialty (pediatric)184
16. Asesores Especializados en Laboratorios, Puebla (AEL)Private laboratoryNot applicable
17. Hospital Aranda de la Parra (Guanajuato)Private 109
18. CARPERMOR. Laboratorio de Referencia Internacional (International Reference Laboratory) Private laboratoryNot applicable
19. Hospital del Niño Morelense (Morelos)Specialty (pediatric)38
20. Instituto Nacional de Enfermedades Respiratorias “Dr. Ismael Cosío Villegas” (Mexico City)Specialty (pulmonology)175
21. Hospital Pediátrico de la Villa (Mexico City)General (pediatric)53
Table
Table 2. Resistance in Escherichia coli and Klebsiella pneumoniae isolates according to ESBL * category.
Table 2. Resistance in Escherichia coli and Klebsiella pneumoniae isolates according to ESBL * category.
Escherichia coli
n = 156		Klebsiella pneumoniae
n = 82
ESBL+ESBL- ESBL+ESBL-p Value **
Total56% (87)44% (69) 52% (43)48% (39)0.62
Antibiotic% Resistant isolates (n)p value% Resistant isolates (n)p value
Ampicillin/
Sulbactam		92 (80)62 (43)0.00003100 (43)35.9 (14)<0.00001
Amikacin1 (1)0 (0)NA2 (1)0 (0)NA
Gentamicin47 (41)23 (15)0.00161 (26)5 (2)<0.00001
Ciprofloxacin95 (83)54 (37)<0.0000188 (38)26 (10)<0.00001
Norfloxacin90 (51)47 (23)<0.0000125 (7)13 (4)0.22
Nitrofurantoin10 (8)6 (4)0.3185(35)50 (19)0.0008
TMP/SMZ63 (53)61 (40)0.7685 (35)13 (5)<0.00001
Fosfomycin14 (12)7 (5)0.197 (3)13 (5)0.3
Chloramphenicol (Kirby–Bauer)26 (23)16 (11)0.1116 (7)15 (6)0.91
* ESBL = extended spectrum beta-lactamase producer. ** Chi-square or Fisher’s exact test if applicable. NA = not applicable.
Table
Table 3. Classification of uropathogens in multidrug-resistant (MDR) and extensively drug-resistant (XDR) bacteria.
Table 3. Classification of uropathogens in multidrug-resistant (MDR) and extensively drug-resistant (XDR) bacteria.
Resistance Characteristic *Escherichia coliKlebsiella pneumoniaep Value
N%N%
Two452930360.22
MDR1066839480.002
XDR5313160.0004
PDR0000-
Total (n)15610082100
* Two: non-susceptible to at least one agent in two antimicrobial categories, MDR: non-susceptible to at least one agent in three or more antimicrobial categories, XDR: non-susceptible to at least one agent in all but two or fewer antimicrobial categories (i.e., bacterial isolates remain susceptible to only one or two categories), and PDR (pandrug-resistant): non-susceptibility to all agents in all antimicrobial categories.
Table
Table 4. Resistance in Escherichia coli and Klebsiella pneumoniae isolates from adult and pediatric patients according to ESBL * category.
Table 4. Resistance in Escherichia coli and Klebsiella pneumoniae isolates from adult and pediatric patients according to ESBL * category.
Escherichia coliKlebsiella pneumoniae
Adult (n = 133)Pediatric (n = 23)Adult (n = 74)Pediatric (n = 8)
ESBL+ESBL-ESBL+ESBL-ESBL+ESBL-ESBL+ESBL-
Total73
(55%)		60
(45%)		14
(61%)		9
(39%)		37
(50%)		37
(50%)		7
(87%)		1
(13%)
AntibioticResistance %
Ampicillin/
sulbactam		9065100441003286100
Amikacin100000280
Gentamicin4823430575860
Ciprofloxacin905593118624430
Nitrofurantoin11700844962100
TMP/SMZ 595893668916620
Fosfomycin5528081300
* ESBL = extended spectrum beta-lactamase producer.
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Share and Cite

MDPI and ACS Style

Miranda-Novales, G.; Flores-Moreno, K.; López-Vidal, Y.; Ponce de León-Rosales, S.; PUCRA Network Members. Limited Therapeutic Options in Mexico for the Treatment of Urinary Tract Infections. Antibiotics 2022, 11, 1656. https://doi.org/10.3390/antibiotics11111656

AMA Style

Miranda-Novales G, Flores-Moreno K, López-Vidal Y, Ponce de León-Rosales S, PUCRA Network Members. Limited Therapeutic Options in Mexico for the Treatment of Urinary Tract Infections. Antibiotics. 2022; 11(11):1656. https://doi.org/10.3390/antibiotics11111656

Chicago/Turabian Style

Miranda-Novales, Guadalupe, Karen Flores-Moreno, Yolanda López-Vidal, Samuel Ponce de León-Rosales, and PUCRA Network Members. 2022. "Limited Therapeutic Options in Mexico for the Treatment of Urinary Tract Infections" Antibiotics 11, no. 11: 1656. https://doi.org/10.3390/antibiotics11111656

Note that from the first issue of 2016, this journal uses article numbers instead of page numbers. See further details here.

Article Metrics

Back to TopTop