Potential Anti-Infectious Activity of Essential Oil Chemotypes of Lippia origanoides Kunth on Antibiotic-Resistant Staphylococcus aureus Strains.

Staphylococcus aureus infections are prevalent in healthcare and community environments. Methicillin-resistant S. aureus is catalogued as a superbug of high priority among the pathogens. This Gram-positive coccus can form biofilms and produce toxins, leading to persistent infection and antibiotic resistance. Limited effective antibiotics have encouraged the development of innovative strategies, with a particular emphasis on resistance mechanisms and/or virulence factors. Medicinal aromatic plants have emerged as promising alternative sources. This study investigated the antimicrobial, antibiofilm, and antihemolysis properties of three different chemotypes of Lippia origanoides essential oil (EO) against susceptible and drug-resistant S. aureus strains. The chemical composition of the EO was analyzed using GC-MS, revealing high monoterpene concentrations, with carvacrol and thymol as the major components in two of the chemotypes. The third chemotype consisted mainly of the sesquiterpene ß-caryophyllene. The MIC values for the two monoterpene chemotypes ranged from 62.5 to 500 µg/mL for all strains, whereas the sesquiterpene chemotype showed activity against seven strains at concentrations of 125-500 µg/mL, which is the first report of its anti-S. aureus activity. The phenolic chemotypes inhibited biofilm formation in seven S. aureus strains, whereas the sesquiterpene chemotype only inhibited biofilm formation in four strains. In addition, phenolic chemotypes displayed antihemolysis activity, with IC50 values ranging from 58.9 ± 3.8 to 128.3 ± 9.2 µg/mL. Our study highlights the importance of L. origanoides EO from the Yucatan Peninsula, which has the potential for the development of anti-S. aureus agents.

Investigating the anti-growth, anti-resistance, and anti-virulence activities of Schoepfia schreberi J.F.Gmel. against the superbug Acinetobacter baumannii.

Schoepfia schreberi has been used in Mayan folk medicine to treat diarrhea and cough. This study aimed to determine the anti-growth, anti-resistance, and/or anti-virulence activities of S. schreberi extracts against Acinetobacter baumannii, a pathogen leader that causes healthcare-associated infections with high rates of drug-resistant including carbapenems, the last line of antibiotics known as superbugs, and analyze their composition using HPLC-DAD. Ethyl acetate (SSB-3) and methanol (SSB-4) bark extracts exhibit antimicrobial and biocidal effects against drug-susceptible and drug-resistant A. baumannii. Chemical analysis revealed that SSB-3 and SSB-4 contained of gallic and ellagic acids derivatives. The anti-resistance activity of the extracts revealed that SSB-3 or SSB-4, combined with imipenem, exhibited potent antibiotic reversal activity against A. baumannii by acting as pump efflux modulators. The extracts also displayed activity against surface motility of A. baumannii and its capacity to survive reactive oxygen species. This study suggests that S. schreberi can be considered a source of antibiotics, even adjuvanted compounds, as anti-resistant or anti-virulence agents against A. baumannii, contributing to ethnopharmacological knowledge and reappraisal of Mayan medicinal flora, and supporting the traditional use of the bark of the medicinal plant S. schreberi for the treatment of infectious diseases.

[Gram-negative bacteria of critical priority in ICU patients from a tertiary care hospital]. / Bacterias Gram-negativas de prioridad crítica en pacientes de las UCI de un hospital de tercer nivel.

Background: Intensive care units (ICU) are the epicenter of antimicrobial resistance (AMR), and patients' infections are mainly caused by Gram-negative bacteria (GNB). Objective: To describe the frequency and trends in AMR of GNB deriving from the clinical samples of ICU patients at a tertiary care hospital in Mérida, Yucatán. Material and methods: Study which included the review of laboratory reports of all bacteriological samples collected from patients admitted to neonatal, pediatric and adult ICU from January 1 2019 to December 31 2021. Results: 433 GNB isolates were recovered, with Klebsiella pneumoniae being the most predominant isolate (n = 117; 27.02%). The majority of GNB were recovered from bronchial secretions (n = 163). Overall, GNB showed high resistance rates to ampicillin (89.48%), ampicillin/sulbactam (66.85%), cephalosporins (58.52-93.81%), tobramycin (58.06%), and tetracycline (61.73%). Among GNB, 73.90% and 68.53% exhibited multidrug-resistant, and highly resistant microorganisms' profiles, respectively, and 47.54% of Acinetobacter baumannii exhibited an extensively drug-resistant profile. A total of 80.33% of A. baumannii was carbapenem-resistant, and 83.76% of K. pneumoniae strains were ESBL-producing. Conclusion: Our data could be helpful to improve the empirical therapy and the infection-control program.

Introducción: las unidades de cuidados intensivos (UCI) son el epicentro de la resistencia a los antimicrobianos (RAM) y las infecciones en estas áreas son causadas principalmente por bacterias Gram-negativas (BGN). Objetivo: describir la frecuencia y los patrones de RAM en BGN aisladas de muestras clínicas de pacientes de las UCI de un hospital de tercer nivel en Mérida, Yucatán. Material y métodos: estudio que incluyó la revisión de los reportes de laboratorio de las muestras bacteriológicas obtenidas de pacientes ingresados en las UCI neonatal, pediátrica y adulta del 1 de enero de 2019 al 31 de diciembre de 2021. Resultados: se identificaron 433 BGN y Klebsiella pneumoniae fue el patógeno más prevalente (n = 117; 27.02%). La mayoría de las BGN aisladas se obtuvieron de secreciones bronquiales (n = 163). En general, las BGN mostraron altas tasas de resistencia a ampicilina (89.48%), ampicilina/sulbactam (66.85%), cefalosporinas (58.52-93.81%), tobramicina (58.06%) y tetraciclina (61.73%). El 73.90% y el 68.53% de las BGN exhibieron perfiles multidrogorresistentes y microorganismos altamente resistentes a fármacos, respectivamente, y 47.54% de los aislamientos de Acinetobacter baumannii mostró perfil de drogorresistencia extendida. El 80.33% de los A. baumannii fue resistente a carbapenémicos y el 83.76% de las K. pneumoniae fueron productoras de BLEE. Conclusión: nuestros datos podrían mejorar la terapia antimicrobiana empírica y el programa de control de infecciones.

Anti-Leishmania activity of the Mayan medicinal plant Thouinia paucidentata Radlk extracts.

Mexico's Yucatan Peninsula is an endemic area of cutaneous leishmaniasis, locally known as the chiclero's ulcer, and Mayan traditional medicine which refers to the use of Thouinia paucidentata Radlk, known as k'an chuunup. Aqueous and organic leaves extracts were evaluated against promastigotes and amastigotes of Leishmania mexicana. Toxicity tests of extracts were performed using Vero and J774A.1 macrophage cell lines. The composition of the most active extracts was analysed by GC-MS. The n-hexane and ethyl acetate extracts showed potent anti-Leishmania activity against the promastigote form, and remarkably, n-hexane extract exhibited potent activity against the amastigote form. Both extracts showed low toxicity on Vero both not on J774A.1 cells. Analysis of both bioactive extracts identified as more abundant compounds, germacrene D-4-ol and thunbergen in n-hexane, and thunbergol in ethyl acetate extracts. Our study presents T. paucidentata as anti-Leishmania phytomedicine supporting its medicinal use and contributes to the understanding of its phytochemical composition.

The Use of Complementary and Alternative Medicine among Peritoneal Dialysis Patients at a Second-Level Hospital in Yucatán Mexico.

BACKGROUND: Complementary and alternative medicine (CAM) is widely used for multiple reasons such as treatment of diseases and their symptoms, empowerment, self-care, disease prevention, dissatisfaction, adverse effects or cost of conventional medicine, perception of compatibility with beliefs, and idiosyncrasy. This study investigated CAM use in patients with chronic kidney disease (CKD) undergoing peritoneal dialysis (PD). METHODS: A cross-sectional survey study was conducted with 240 eligible patients with CKD in the PD program. By applying the I-CAM-Q-questionnaire, the frequency, level of satisfaction, and reasons for CAM use were explored, and the demographic and clinical data of users and non-users were analyzed. Data analysis included descriptive analysis, Student's t-test, Mann-Whitney U, chi-square, and Fisher tests. RESULTS: The main types of CAM used were herbal medicine, and chamomile was the most commonly used. To improve the state of well-being was the main reason for use, the attributable benefit of CAM was high, and only a low percentage of users reported side effects. Only 31.8% of the users informed their physicians. CONCLUSION: The use of CAM is popular among renal patients, and physicians are not adequately informed; in particular, the CAM type ingested represents a risk for drug interactions and toxicity.

Antimicrobial potential of the Mayan medicine plant Matayba oppositifolia (A. Rich.) Britton against antibiotic-resistant priority pathogens.

ETHNOPHARMACOLOGICAL RELEVANCE: The bark of Matayba oppositifolia (A. Rich.) Britton (commonly known as "huaya" or "palo huacax") is commonly utilized in traditional Mayan medicine for treating diarrhea and for canker and other sores. AIM OF THE STUDY: The aim of this study was to investigate the in-vitro antimicrobial activity of M. oppositifolia bark extracts against drug-susceptible and -resistant ESKAPE-E pathogens. In addition, the phytochemical composition of the best antibacterial extract was analyzed. MATERIALS AND METHODS: The bark extracts were prepared with different solvents, including water, n-hexane, ethyl acetate and methanol. These were tested against ESKAPE-E (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacter spp., including Escherichia coli) strains using Resazurin Microtiter Assay. In addition, the composition of the most active extract was analyzed by GC-MS. RESULTS: The aqueous and organic bark extracts showed activity on drug-susceptible and -resistant ESKAPE-E microbes (MIC = 1000-31.25 µg/mL). The n-hexane bark extract was more active against the superbugs carbapenem-resistant K. pneumoniae (MIC = 500-31.25 µg/mL) and A. baumannii (MIC = 250-125 µg/mL). The GC-MS analysis of this extract allowed the identification of 12 phytochemicals as the potential antibacterial compounds. The major compounds identified were palmitic acid (1), friedelan-3-one (2) and 7-dehydrodiosgenin (3). CONCLUSION: The present study reveals the strong in-vitro antibacterial activity of the n-hexane extract from the bark of M. oppositifolia and demonstrates the potential of natural products as a source of antibacterial compounds or phytomedicines that are specifically effective against drug-resistant ESKAPE-E bugs. Additionally, our investigation contributes to the ethnopharmacological knowledge and reappraisal of Mayan medicinal flora, as well as supports the traditional use of the bark of the medicinal plant M. oppositifolia for the treatment of infectious diseases.

Efficacy of Fosfomycin against Planktonic and Biofilm-Associated MDR Uropathogenic Escherichia coli Clinical Isolates.

Urinary tract infections (UTI) are a severe public health problem and are caused mainly by the uropathogenic Escherichia coli (UPEC). Antimicrobial resistance and limited development of new antimicrobials have led to the reuse of old antibiotics such as fosfomycin. The aim of this study was to evaluate the in vitro efficacy of fosfomycin on a collection of multidrug-resistant (MDR) UPEC and the degradative activity on biofilm producers. A total of 100 MDR UPEC clinical isolates were collected from patients at Mexican second- and third-level hospitals. Microorganism identification was performed using an automated system, the evaluation of the susceptibility of clinical isolates to fosfomycin was performed using the resazurin microtiter assay, and the identification of biofilm producers and the effect of fosfomycin in biofilms were evaluated using the crystal violet method. Among planktonic MDR UPEC, 93% were susceptible to fosfomycin. Eighty-three MDR UPEC were categorized as weak (39.8%), moderate (45.2%), and strong (14.5%) biofilm producers. Fosfomycin exhibited degradative activity ranging from 164.4 µg/mL to 1045 µg/mL. Weak producers required statistically lower concentrations of fosfomycin to destroy the biofilm, contrary to moderate and strong producers. In conclusion, fosfomycin could be an option for the treatment of infections caused by MDR UPEC, for which the antimicrobial treatment is more often becoming limited.

The Alpha Variant (B.1.1.7) of SARS-CoV-2 Failed to Become Dominant in Mexico.

During the coronavirus disease 2019 (COVID-19) pandemic, the emergence and rapid increase of the B.1.1.7 (Alpha) lineage of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), first identified in the United Kingdom in September 2020, was well documented in different areas of the world and became a global public health concern because of its increased transmissibility. The B.1.1.7 lineage was first detected in Mexico during December 2020, showing a slow progressive increase in its circulation frequency, which reached its maximum in May 2021 but never became predominant. In this work, we analyzed the patterns of diversity and distribution of this lineage in Mexico using phylogenetic and haplotype network analyses. Despite the reported increase in transmissibility of the B.1.1.7 lineage, in most Mexican states, it did not displace cocirculating lineages, such as B.1.1.519, which dominated the country from February to May 2021. Our results show that the states with the highest prevalence of B.1.1.7 were those at the Mexico-U.S. border. An apparent pattern of dispersion of this lineage from the northern states of Mexico toward the center or the southeast was observed in the largest transmission chains, indicating possible independent introduction events from the United States. However, other entry points cannot be excluded, as shown by multiple introduction events. Local transmission led to a few successful haplotypes with a localized distribution and specific mutations indicating sustained community transmission. IMPORTANCE The emergence and rapid increase of the B.1.1.7 (Alpha) lineage of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) throughout the world were due to its increased transmissibility. However, it did not displace cocirculating lineages in most of Mexico, particularly B.1.1.519, which dominated the country from February to May 2021. In this work, we analyzed the distribution of B.1.1.7 in Mexico using phylogenetic and haplotype network analyses. Our results show that the states with the highest prevalence of B.1.1.7 (around 30%) were those at the Mexico-U.S. border, which also exhibited the highest lineage diversity, indicating possible introduction events from the United States. Also, several haplotypes were identified with a localized distribution and specific mutations, indicating that sustained community transmission occurred in the country.

Activity of Semi-Synthetic Mulinanes against MDR, Pre-XDR, and XDR Strains of Mycobacterium tuberculosis.

Tuberculosis causes more than 1.2 million deaths each year. Worldwide, it is the first cause of death by a single infectious agent. The emergence of drug-resistant strains has limited pharmacological treatment of the disease and today, new drugs are urgently needed. Semi-synthetic mulinanes have previously shown important activity against multidrug-resistant (MDR) Mycobacterium tuberculosis. In this investigation, a new set of semi-synthetic mulinanes were synthetized, characterized, and evaluated for their in vitro activity against three drug-resistant clinical isolates of M. tuberculosis: MDR, pre-extensively Drug-Resistant (pre-XDR), and extensively Drug-Resistant (XDR), and against the drug-susceptible laboratory reference strain H37Rv. Derivative 1a showed the best anti-TB activity (minimum inhibitory concentration [MIC] = 5.4 µM) against the susceptible strain and was twice as potent (MIC = 2.7 µM) on the MDR, pre-XDR, and XDR strains and also possessed a bactericidal effect. Derivative 1a was also tested for its anti-TB activity in mice infected with the MDR strain. In this case, 1a produced a significant reduction of pulmonary bacilli loads, six times lower than the control, when tested at 0.2536 mg/Kg. In addition, 1a demonstrated an adjuvant effect by shortening second-line chemotherapy. Finally, the selectivity index of >15.64 shown by 1a when tested on Vero cells makes this derivative an important candidate for future studies in the development of novel antitubercular agents.

Two New Dihydrosphingosine Analogs Against Mycobacterium tuberculosis Affect gltA1, lprQ, and rpsO Expression.

The emergence of multidrug-resistant (MDR) Mycobacterium tuberculosis strains threaten the control of tuberculosis. New antitubercular dihydrosphingosine analogs, named UCIs, have been evaluated in preclinical studies but their cellular and molecular mechanisms of action against M. tuberculosis are still unknown. The aim of this study was to evaluate the effect of UCI exposure on gene expression of drug-sensitive H37Rv and MDR CIBIN:UMF:15:99 clones of M. tuberculosis which were isolated, phenotypically, and genetically characterized, cultured to log phase and treated with UCI compounds; followed by total RNA isolation, reverse transcription and hybridization assays on Affymetrix genomic microarrays. Data were validated with RT-qPCR assays. As results, UCI-05 and UCI-14 exposure increased gltA1 expression in drug-sensitive H37Rv clones. Furthermore, UCI-05 increased lprQ expression in MDR CIBIN:UMF:15:99 M. tuberculosis clones while UCI-14 reduced the expression of this gene in drug-sensitive H37Rv clones. In addition, UCI-05 reduced rpsO expression in drug-sensitive H37Rv clones. We found gene expression alterations that suggest these molecules may alter carbon and lipid metabolism as well as interfere in the protein-producing machinery in M. tuberculosis.

Antibacterial and antibiofilm activities of Mayan medicinal plants against Methicillin-susceptible and -resistant strains of Staphylococcus aureus.

ETHNOPHARMACOLOGICAL RELEVANCE: Several medicinal plants are used in Mayan Traditional Medicine to treat skin, urinary, respiratory, and gastrointestinal infectious diseases. However, scientific studies that have supported the bioactivity of these Mayan medicinal plants are limited. AIM OF THE STUDY: To assess the in-vitro anti-Staphylococcus aureus growth and biofilm-formation activities of 15 Mayan medicinal plants that were selected based on their traditional uses for the treatment of infectious diseases. MATERIALS AND METHODS: Mayan medicinal plants used traditionally to treat infectious diseases were preselected. For each part of the plants, four extracts were prepared with different solvents (water, n-hexane, ethyl acetate, and methanol). These were tested against two reference strains: a Methicillin-susceptible and -resistant S. aureus, and two clinical isolates, including a susceptible and multidrug-resistant S. aureus using a Resazurin Microtiter Assay. In addition, the plant extracts were evaluated in biofilm-formation inhibition on S. aureus by means of the Crystal Violet method. RESULTS: A total of 120 extracts from 15 Mayan medicinal plant species belonging to 12 different families were selected according their ethnopharmacological uses to treat infectious diseases. Among the selected plant species, 26 extracts obtained from eight medicinal Mayan plants exhibited significant anti-S. aureus against the four strains tested. The most active extracts were the Aq (aqueous) leaf extract of Krugiodendron ferreum (Minimal Inhibitory Concentration [MIC] = 125-250 µg/mL), the MeOH bark extracts of Matayba oppositifolia, Clusia flava, Gymnopodium floribundum, the MeOH leaf extract of Spondias purpurea with MIC values of 250 µg/mL, and the MeOH leaf and Aq bark extracts of K. ferreum (MIC = 250-500 µg/mL). Among the active extracts, 12 exhibited a bactericidal effect on S. aureus strains (Minimal Bactericidal Concentration [MBC] = 250-1000 µg/mL). Forty extracts from 13 plants have an effect on the anti-formation of biofilm, the most active were the MeOH leaf extract of M. oppositifolia (one-half Inhibitory Concentration [IC50] = 10.4 µg/mL) and the MeOH (IC50 = 17.7 µg/mL) and Hex (18.2 µg/mL) leaf extracts from S. purpurea. CONCLUSION: Aqueous and organic extracts from Mayan medicinal plants showed bactericidal and anti-biofilm activities even against drug-resistant S. aureus strains. The present study supports the traditional usage of some plants employed in Mayan medicine for illnesses such as skin, gastrointestinal, and urinary infections and suggest that these plants could be a good source of antibacterial phytochemicals.

Isolation and Histopathological Changes Associated with Non-Tuberculous Mycobacteria in Lymph Nodes Condemned at a Bovine Slaughterhouse.

Background: non-tuberculous mycobacteria (NTM) infect humans and animals and have a critical confounding effect on the diagnosis of bovine tuberculosis. The Official Mexican Standard (Norma Oficial Mexicana, NOM-ZOO-031-1995) for food safety regulates Mycobacterium bovis in cattle, but not the NTM species. The study's objective was to isolate and identify the NTM present in condemned bovine lymph nodes in a slaughterhouse, characterize the histological lesions, and correlate bacteriological and microscopic findings with the antemortem tuberculin skin test. Methods: from 528 cattle, one or two pooled samples of lymph nodes from each animal were cultured for Mycobacteria spp. and processed for histopathology. Results: mycobacteria were isolated from 54/528 (10.2%) of the condemned lymph nodes; 25/54 (46.2%) of these isolates were NTM; 4 bacteriological cultures with fungal contamination were discarded. Granulomatous and pyogranulomatous inflammation were present in 6/21 (28.6%) and 7/21 (33.3%) of the NTM-positive lymph nodes, respectively. The species of NTM associated with granulomatous lymphadenitis were M. scrofulaceum, M. triviale, M. terrae, and M. szulgai, while those causing pyogranulomatous lesions were M. szulgai, M. kansasii, M. phlei, and M. scrofulaceum. Conclusions: the NTM infections can cause false-positive results in the tuberculin test because of cross immune reactivity and interference with the postmortem identification of M. bovis in cattle.

Mulinane- and Azorellane-Type Diterpenoids: A Systematic Review of Their Biosynthesis, Chemistry, and Pharmacology.

Mulinane- and azorellane-type diterpenoids have unique tricyclic fused five-, six-, and seven-membered systems and a wide range of biological properties, including antimicrobial, antiprotozoal, spermicidal, gastroprotective, and anti-inflammatory, among others. These secondary metabolites are exclusive constituents of medicinal plants belonging to the Azorella, Laretia, and Mulinum genera. In the last 30 years, more than 95 mulinanes and azorellanes have been reported, 49 of them being natural products, 4 synthetics, and the rest semisynthetic and biotransformed derivatives. This systematic review highlights the biosynthetic origin, the chemistry, and the pharmacological activities of this remarkably interesting group of diterpenoids.

In vitro growth inhibition and bactericidal activity of spathulenol against drug-resistant clinical isolates of Mycobacterium tuberculosis

ABSTRACT Spathulenol was isolated from an extract of Azorella compacta Phil., Apiaceae, by various chromatographic method; identification of the chemical structure was confirmed by comparing its spectroscopic data with those reported in the literature. The anti-Mycobacterium tuberculosis activity of spathulenol was evaluated on MDR, pre-XDR, and XDR clinical isolates of M. tuberculosis, as well as on the reference susceptible strain H37Rv and its cytotoxic activity was evaluated on the Vero Cell Line. The anti-M. tuberculosis activity of spathulenol was twice as potent against the MDR, pre-XDR, and XDR clinical isolates (6.25 µg/ml) than on the susceptible H37Rv strain (12.5 µg/ml). Additionally, the anti-M. tuberculosis activity shown by spathulenol was established as bactericidal on drug-resistant and susceptible strains of M. tuberculosis. Finally, cytotoxic activity on the Vero cell line (CC50 = 95.7 µg/ml) indicated that spathulenol is a selective anti-M. tuberculosis compound, with a selective index of 15.31 against drug-resistant clinical isolates of M. tuberculosis.

Antitubercular Activity of the Fungus Gliocladium sp. MR41 Strain.

Tuberculosis (TB) is a leading cause of death worldwide from infectious diseases and its inadequate treatment has led to emergence of resistant strains. The emergence of these strains renders the search for new drugs for the treatment of TB. The aim of this study was the evaluation of the anti-TB activity of the extract from fungus Gliocladium sp. MR41, and bioassay-guided fractionation and identification of majority compounds was carried out. Fungal strain culture was lyophilized and extracted by maceration in Ethyl Acetate (EtOAc). This extract was fractionated by liquid-liquid partitioning and chromatographic techniques, and the compounds were identified by their spectroscopic data. Furthermore, the EtOAc extract, fractions, and pure compounds were tested on Mycobacterium tuberculosis using the Microplate Alamar Blue Assay. From the bioactive AcetoNitrile Fraction (AcNF; MIC = 3.13 µg/mL) of the EtOAc extract, four compounds were isolated: ergosterol (1), ergosterol-5, 8-peroxide (2), 1, 6-di-O-acetyl-2,3,4,5-tetrahydroxy-hexane (3), and allitol (4). Only 2 exhibited potent activities against M. tuberculosis (MIC = 0.78 µg/mL). Additionally, this is the first report, to our knowledge, of polyols 3 and 4 from this fungus.

High Prevalence of Antimicrobial Resistance Among Gram-Negative Isolated Bacilli in Intensive Care Units at a Tertiary-Care Hospital in Yucatán Mexico.

Background and Objectives: Antimicrobial resistance (AMR) is increasing worldwide and imposes significant life-threatening risks to several different populations, especially to those in intensive care units (ICU). The most commonly isolated organisms in ICU comprise gram-negative bacilli (GNB), and these represent a leading cause of serious infections. This study was conducted to describe the prevalence of resistance in GNB isolated from patients in adults, pediatric, and neonatal ICU in a tertiary-care hospital in Mérida, Mexico. Materials and Methods: A retrospective study was done on samples collected in Neonatal (NICU), Pediatric (PICU) and Adult (AICU) ICU of Unidad Médica de Alta Especialidad, Instituto Mexicano del Seguro Social in Mérida, México. The identification of isolates and antimicrobial susceptibility testing were performed using an automated system. Results: A total of 517 GNB strains were isolated. The most common positive culture was bronchial secretions. Pseudomonas aeruginosa was the prevalent pathogen in NICU and PICU, whereas Escherichia coli was common in the AICU. Overall, GNB exhibited a high resistance rates for Ampicillin (95.85%), Cefuroxime (84.17%), Piperacillin (82.93%), Cefotaxime (78.07%), Ceftriaxone (77.41%), Aztreonam (75.23%), Cefazolin (75.00%), and Ceftazidime (73.19%). There are significant differences in the resistance rates of GNB from different ICUs for penicillins, cephalosporins, carbapenems and fluoroquinolones drugs. Escherichia coli (multidrug-resistant [MDR] = 91.57%, highly resistant microorganisms [HRMO] = 90.36%) and Acinetobacter baumannii (MDR = 86.79%, HRMO = 83.02%) exhibited the highest percentage of MDR and HRMO profiles. The prevalence of the extended-spectrum beta-lactamases (ESBL)-producing isolates was 83.13% in E. coli, 78.84% in Klebsiella pneumoniae, and 66.67% in Proteus mirabilis, respectively. Conclusions: The high resistance rates to drugs were exhibited by our GNB isolates. Continuous surveillance and control of the use of antimicrobials are urgently needed to reduce the emergence and spreading of MDR, HRMO, and/or ESBL-producing bacilli.

Bactericidal Effect of the Leaf Extract from Musa spp. (AAB Group, Silk Subgroup), cv. "Manzano" Against Multidrug-Resistant Mycobacterium tuberculosis.

Air-dried leaves of a Musa spp. AAB, cv. "Manzano" plant, known as Ja'as in the Maya culture, were sequentially extracted with hexane, ethyl acetate, and methanol; the resulting extracts were investigated for their antimycobacterial activity against susceptible and drug-resistant strains of Mycobacterium tuberculosis (MTB) using the Microplate Alamar Blue Assay. Both the n-hexane extract (HE) and ethyl acetate extract (EE) showed potent activity against both strains of MTB, with the EE exhibiting the strongest activity and a Minimum Inhibitory Concentration of 12.5 and 6.25 µg/mL against susceptible and drug-resistant strains, respectively. Both extracts also demonstrated a mycobactericidal effect and a very good selectivity index when tested for cytotoxic activity on Vero monkey kidney cells, using the Sulforhodamine B assay. Our results demonstrate the efficiency and selectivity of Musa spp. AAB, cv. "Manzano" against MTB strains and support its traditional use as remedy against tuberculosis in Maya traditional medicine.

Diabetes screen during tuberculosis contact investigations highlights opportunity for new diabetes diagnosis and reveals metabolic differences between ethnic groups.

Type 2 diabetes (T2D) is a prevalent risk factor for tuberculosis (TB), but most studies on TB-T2D have focused on TB patients, been limited to one community, and shown a variable impact of T2D on TB risk or treatment outcomes. We conducted a cross-sectional assessment of sociodemographic and metabolic factors in adult TB contacts with T2D (versus no T2D), from the Texas-Mexico border to study Hispanics, and in Cape Town to study South African Coloured ethnicities. The prevalence of T2D was 30.2% in Texas-Mexico and 17.4% in South Africa, with new diagnosis in 34.4% and 43.9%, respectively. Contacts with T2D differed between ethnicities, with higher smoking, hormonal contraceptive use and cholesterol levels in South Africa, and higher obesity in Texas-Mexico (p < 0.05). PCA analysis revealed striking differences between ethnicities in the relationships between factors defining T2D and dyslipidemias. Our findings suggest that screening for new T2D in adult TB contacts is effective to identify new T2D patients at risk for TB. Furthermore, studies aimed at predicting individual TB risk in T2D patients, should take into account the heterogeneity in dyslipidemias that are likely to modify the estimates of TB risk or adverse treatment outcomes that are generally attributed to T2D alone.

Efficacious In Vitro and In Vivo Effects of Dihydrosphingosine-Ethambutol Analogues Against Susceptible and Multi-drug-resistant Mycobacterium tuberculosis.

BACKGROUND AND AIMS: Tuberculosis (TB) is a major worldwide health problem in part due to the lack of new drugs and the emergence of multidrug-resistant strains (MDR). The aim of this study was to select anti-tuberculosis drug candidates from a collection of 69 synthetic sphingosine-ethambutol analogues through in vitro and in vivo evaluations. METHODS: The 69 compounds were evaluated in vitro against two Mycobacterium tuberculosis strains, a drug susceptible (H37Rv) and a MDR clinical isolate (CIBIN-99). Four selected compounds, those that exhibited the highest potency in vitro, were tested in vivo using a model of progressive TB in BALB/c mice infected with the drug susceptible strain, either alone or combined with conventional chemotherapy, as well as in mice infected with the MDR strain. The acute toxicity was evaluated on male and female adult BALB/c mice. RESULTS: Ten of the evaluated compounds resulted more potent in vitro than ethambutol. The experimental compound 2b (2-aminopalmitol benzyl ether) was the most efficacious and also showed additive effects in combination with conventional chemotherapy. It did not exhibit toxicity (LD50 >2000 mg/kg). CONCLUSIONS: Compound 2b can be considered as a new drug candidate to continue its development against M. tuberculosis MDR strains.

Therapeutic efficacy of liposomes containing 4-(5-pentadecyl-1,3,4-oxadiazol-2-yl)pyridine in a murine model of progressive pulmonary tuberculosis.

BACKGROUND AND OBJECTIVES: Tuberculosis (TB) is one of the deadliest infectious diseases and comprises a global public health concern because co-infection with Human immunodeficiency virus (HIV) and, in particular, the continuous isolation of new Multidrug-resistant strains (MDR), rendering the discovery of novel anti-TB agents a strategic priority. One of the most effective first-line mycobactericidal drugs is Isoniazid (INH). Previously, we reported in vitro anti-mycobacterial activity against sensitive and MDR Mycobacterium tuberculosis strains of a new oxadiazole obtained from the hybridization of INH and palmitic acid. The present study evaluated the therapeutic potential of liposomes including Phosphatidylcholine (PC) and L-α Phosphatidic acid (PA) or PC and Cholesterol (Chol) containing 4-(5-pentadecyl-1,3,4-oxadiazol-2-yl)pyridine in BALB/c male mice infected by intratracheal (i.t.) route with drug-sensitive or MDR M. tuberculosis. METHODS: The lipophilic 4-(5-pentadecyl-1,3,4-oxadiazol-2-yl)pyridine was obtained to mix INH and palmitoyl chloride. The in vivo anti-TB effect of this oxadiazole derivative contained in two different liposomes was tested in BALB/c mice infected with a sensitive strain of M. tuberculosis, initiating treatment 2 months post-infection, by i.t. route, of 50 µg of oxadiazole derivative for 1 month. In a second stage, mice were infected with an MDR (resistant to first-line drugs) and treated with 150 µg of an oxadiazole derivative carried by PC + Chol liposomes for 2 months. The effect of the oxadiazole derivative in vivo was determined by the quantification of lung bacilli loads and histopathology. RESULTS: In comparison with control animals, drug-sensitive, strain-infected mice treated for 1 month with 50 µg of this oxadiazole derivative contained in the liposomes of PC + Chol showed a significant, 80% decrease of live bacilli in lungs, which correlated with the morphometric observation, and the group of MDR clinical isolate-infected mice treated with 150 µg of the oxadiazole derivative contained in the same type of liposome showed significantly lower lung bacillary loads than control mice, producing 90% of bacilli burden reduction after 2 months of treatment. CONCLUSION: These results confirm and extend the reported highly efficient anti-mycobacterial activity of this lipophilic oxidazole derivative when it is carried by liposomes in mice suffering from late progressive pulmonary TB induced by drug-sensitive, and most prominently by, MDR strains.